Chinese Clinical Oncology

The inhibitory effect of CL-387785 on the invasion and metastasis of T790M EGFR mutant H1975 cells and its sensitization of radiotherapy

SHENG Zhaoying， CAI Yong， NI Jian.

Chinese Clinical Oncology. 2015, 7 (7): 577.

Abstract ( 962 )

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Objective To investigate the inhibitory effect of CL-387785 on the invasion and metastasis of EGFR T790M mutant H1975 cells and its sensitization of radiotherapy. Methods The H1975 cell was treated with 0，10， 25， 50， 100 nmol/L CL-387785. The MTT colorimetric assay was used to detect the proliferation inhibition rates at 24，48，72 and 96 h after treatment. Moreover，Annexin-FITC/PI double staining method via flow cytometry was used to detect the apoptotic rates of different concentrations of CL-387785 at 48 and 96 h. Changes of invasion and migration of H1975 cells treated with CL-387785 were detected by Transwell and scratch assay， respectively. The clone formation assay was employed to investigate the survival fraction（SF） of the H1975 cells after exposure to CL-387785 following different doses of X-ray （0， 2， 4， 6， 8 and 10 Gy） irradiation. The target model was fitted to the cell survival curve to calculate the sensitization enhancement ratio （SER）. Results CL-387785 inhibited the proliferation of H1975 cells， and dose- and time-dependently increased the inhibition rates of the proliferation in range of 10-100 nmol/L. CL-387785 could induce the apoptosis and decrease the number of penetrate-membrane cell and migration distance of H1975 cells in a dose-dependent manner （P＜0.05）. In the 2-10 Gy irradiation range， the SF of 10， 25， 50 and 100 nmol/L CL-387785 were lower than that of 0 nmol/L，and SF decreased with the increase of concentration of CL-387785 and above differences were statistically significant （P＜0.05）. Compared with the 0 nmol/L CL-387785， the SER of 25， 50， 10， 100 nmol/L CL-387785 SER after treatment were 1.17， 1.39， 2.88 and 3.64， respectively. Conclusion The irreversible EGFR inhibitor CL-387785 can inhibit the invasion and metastasis of T790M EGFR mutant H1975 cells and has the effect of radiation sensitization.

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Wnt/β-catenin signaling pathway regulates stemness of non-small cell lung cancer cell NCI-H23

ZHAO Zhili，HAN Yali.

Chinese Clinical Oncology. 2015, 7 (7): 583.

Abstract ( 990 )

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Objective To explore the effect of Wnt/β-catenin signaling pathway on stemness maintenance in NCI-H23 cell. Methods The NCI-H23 was treated with the GSK-3β inhibitor （CHIR-99021） or β-catenin siRNA. Then， the MTT assay， stem cell culture， wound healing assay and Western blotting were used to detect proliferation ability， sphering ability and migration ability，respectively. Results Compared with control， there were increased proliferation ability and spher rate in NCI-H23 cell after treatment with CHIR-99021 for 24 h （P＜0.05）. Wound healing showed that the CH-treated cells were also faster than non-treatment. Meanwhile， CH-treated cells appeared to exhibit a declined level of p-GSK-3β. The expression of proliferating cell nuclear antigen，CD133，aldehyde dehydrogenase 1A1，Nanog and matrix metalloproteinase-2 showed a significantly enhance in both of NCI-H23 and NCI-H23 stem cell. After silencing β-catenin with β-catenin siRNA， the expression of CD133， ALDH1A1 and Nanog were declined and the sphere rate was decreased comparing with control. Conclusion Wnt/β-catenin signaling pathway involved in regulation of stemness in NCI-H23 cell.

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Expression of miR-133 in gastric cancer tissues and its effect on malignant behavior of human gastric cancer cells

XU Ronghua， HE Donglei， MENG Jin.

Chinese Clinical Oncology. 2015, 7 (7): 588.

Abstract ( 883 )

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Objective To investigate the expression of microRNA-133（miR-133） in gastric cancer tissues and cell lines as well as its effect on apoptosis and invasion of gastric cancer cells. Methods The real-time quantitative PCR （qPCR） was used to detect the miR-133 level in 64 cases of gastric cancer tissues and corresponding adjacent normal tissues. Then， we analyzed the relationship between miR-133 expression and clinical pathological parameters（age， gender， tumor location， clinical stage， differentiation degree， invasion depth and lymph node metastasis）. The expression of miR-133 was detected in gastric cancer cell line AGS， SGC-7901， MKN-1， MKN-45， MGC-803， BGC-823 and GES-1， and the normal gastric mucosa cell line， GES-1， was used as the control. The gastric cancer cell with the lowest level of miR-133 was chosen for the transfection with the recombinant plasmid pCDNA3.1+miR-133. PI/Annexin V double staining and Transwell assay were used to detect the effect of miR-133 on apoptosis and invasion of cells. Results The relative expression of miR-133 in gastric carcinoma tissues was 0.347±0.024， lower than that of the adjacent tissues （P＜0.05）. Its expression was related to clinical stage， differentiation， depth of invasion and lymph node metastasis （P＜0.05）. Compared with the GES-1 cells， the miR-133 levels of gastric cancer cells were lower （P＜0.05）， and the expression level of MKN-45 was lowest. Compared with other two groups at 48 and 96 h after transfection， the apoptosis level was higher but the number of the cells was decreased in the overexpression group （P＜0.05）. Conclusion miR-133 was lowly expressed in gastric cancer tissues and cells， and upregulation of miR-133 can inhibit the invasion and apoptosis of gastric cancer cells.

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Experimental study of apoptosis of human breast cancer MDA-MB-231 cell line induced by AZD2281

LUO Xiang，SHI Yanxia，JIANG Wenqi，LI Zhiming，XIA Qing.

Chinese Clinical Oncology. 2015, 7 (7): 593.

Abstract ( 764 )

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Objective To investigate the effects of AZD2281 on proliferation and apoptosis of human breast cancer cell MDA-MB-231 in vitro and the possible mechanisms. Methods Different concentrations of AZD2281（2.5, 5, 10 nmol/L） were used to treat MDA-MB-231 cells for 24，48，72 h， and its effects of time and dose were observed. Cell proliferation inhibition rates were measured by MTT assay. The flow cytometry was used to analyze cell-cycle distribution and cell apoptosis. The western blotting was used to detect the expression levels of Bcl-2 and caspase-3. Results The proliferation of MDA-MB-231 cells was inhibited by AZD2281 in a dose-and time-dependent manner. The cell was arrested in the G0/G1 phase by AZD2281 treatment after 24 h， and the cell apoptosis was induced in a dose-dependent manner. AZD2281 could down-regulate the protein expression of Bcl-2 level after treatment with AZD2281 but up-regulate the protein expression level of caspase-3 protein. Conclusion AZD2281 can inhibit the proliferation of human breast cancer cell MDA-MB-231 and induce its apoptosis by down-regulating the expression of Bcl-2 protein and up-regulating the expression of caspase-3 protein.

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Effects of matrine on proliferation，apoptosis and PI3K/Akt pathway of cultured retinoblastoma cells

CHEN Yao，AI Ming.

Chinese Clinical Oncology. 2015, 7 (7): 598.

Abstract ( 748 )

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Objective To investigate the effect of matrine（Mat） on the proliferation， apoptosis and PI3K/Akt pathway of retinoblastoma（Rb） cells. Methods Rb cell lines Y79 cells were cultured with different concentration of Mat（0.5， 1.0， 1.5g/L）. Cell proliferation and apoptosis were determined by CCK-8 assay and flow cytometry（stained with Annexin V-FITC/PI）. Apoptosis related genes Bax and Bcl-2， as well as the expression of phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） pathways protein， including p85α，p-Aktser473and Akt， were determined by Western blotting. Results Mat could inhibit cell proliferation and induce apoptosis in a dose-dependent manner， respectively. Moreover， Mat increased the expression of Bax， but decreased the Bcl-2 protein expression. Results of Western blotting showed that Mat decreased the level of PI3K p85α and phosphor-Akt. Conclusion Mat could inhibit the proliferation and induce the apoptosis of Rb cells， probably modulating by the PI3K/Akt pathway.

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The effect of megestrol acetate in combination with arsenic trioxide on growth of HepG2 cells

LI Chuanxiang， FU Xing， TIAN Geng.

Chinese Clinical Oncology. 2015, 7 (7): 602.

Abstract ( 752 )

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Objective To investigated the anti-tumor effects of megestrol acetate （MA） in combination with arsenic trioxide （As2O3） in hepatocellular carcinoma （HCC）. Methods The HepG2 cells were divided into 4 groups： treated with MA （75 μmol/L） alone， As2O3（1.0 μg/ml）alone， or MA （75 μmol/L） in combination with As2O3（1.0 μg/ml）and negative control group for 24 h. The doses of the drugs were confirmed according to our previous researches. The effect of MA combined with As2O3 on HepG2 cell growth was detected by Cell Counting Kit method （CCK-8） and flow cytometry assay. The expressive effect of X-linked inhibitor of apoptosis protein（XIAP） in HepG2 cells was analyzed with Western blotting. Results CCK-8 assay showed MA combined with As2O3 could significantly inhibit the growth of HepG2 cells compared with MA or As2O3 alone. The apoptotic rate of MA combined with As2O3 group was significantly higher than those of MA or As2O3 group. Compared with MA or As2O3 group， MA combined with As2O3 significantly decreased the expression of apoptosis-related proteins XIAP.

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Expression of Latexin and its clinicopathological significance in esophageal squamous cell carcinoma

GU Xiaoqiang， WU Qing.

Chinese Clinical Oncology. 2015, 7 (7): 607.

Abstract ( 767 )

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Objective To investigate the clinical significance of Latexin（LXN） in esophageal squamous cell carcinoma（ESCC）. Methods In this study， 183 cases of ESCC tissues and para-carcinoma tissues were evaluated for LXN expression by tissue microarray and immunohistochemistry. The relationship between the expression of LXN and clinical parameters（tumor size， T staging, N stagings, differentiation and TNM staging） and prognosis were analyzed. Results The positive rate of LXN expression was 48.6% in ESCC tissues， lower than 100.0% in para-carcinoma tissues. A significant correlation was observed between the expression of LXN and tumor size， T staging, N staging， tumor differentiation and TNM staging. Patients with LXN positive expression had longer overall survival than those without LXN expression. Conclusion LXN was down-regulated with the development and progression of ESCC and loss of LXN expression is associated with the poor prognosis of ESCC.

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The expression of CHIP in human breast cancer and its clinical significance

WANG Huan， WANG Jie， LIU Fei， GUO Feng.

Chinese Clinical Oncology. 2015, 7 (7): 611.

Abstract ( 774 )

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Objective To investigate the expression of carboxyl teminus of Hsc70-interacting protein （CHIP） in human breast cancer and its clinical significance. Methods Expression of CHIP was detected by the immunohistochemistry in 128 cases of breast cancer specimens. The CHIP expression in breast cancer and its relationship with clinicopathological features and molecular types were analyzed using non-parametric statistical test method. Results The positive rate of CHIP in breast cancer was 60.2%； and the positive rate in clinical stage Ⅲ-Ⅳ was 43.2%， which was significantly lower than 67.0% in stageⅠ-Ⅱ（P＜0.05）. CHIP positive expression rate in cases with lymph node metastasis was lower than that of patients without lymph node metastasis （P＜0.05）. CHIP positive expression rates of Luminal A subtype， Luminal B subtype， HER-2 subtype and Basal-like subtype patients were 66.7%， 70.5%， 50.0% and 44.0%，repectively （P＜0.05）. The level of expression of CHIP has no significant difference with age， histological grade， tumor size, distant metastasis or HER-2 status. Conclusion The expression of CHIP may relate to tumorgenesis and development， and it might be used as a predictor of recurrent risk.

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Expression and clinical significance of Skp2 and p27 in the tissues of esophageal carcinoma

YE Jinjun， FEI Chunming， ZHOU Guoren， HUANG Kewei， JIANG Ming， ZHANG Zhi， SUN Lei.

Chinese Clinical Oncology. 2015, 7 (7): 614.

Abstract ( 795 )

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Objective To investigate the expression and clinical significance of S-phase kinase-associated protein 2（Skp2） and p27 in the esophageal carcinoma. Methods Immunohistochemistry method was used to detect expression of Skp2 and p27 in 82 cases of esophageal carcinoma and 10 cases of normal esophageal epithelial tissue adjacent to esophageal cancer. The correlation between expressions of Skp2 and p27 protein with clinicopathological features was analyzed by chi-square test. Correlation analysis was made by Spearman correlation analysis. Results Positive rates of Skp2 and p27 were 67.07%（55/82） and 35.37%（29/82） in esophageal carcinoma, significant different from 20.00%（2/10） and 90.00%（9/10） in normal tissues（P＜0.01）. Skp2 expression was not associated with gender， age and tumor site， but with differentiation grades， the depth of tumor invasion， lymph node metastasis and clinical TNM stages（P＜0.05）； p27 expression was not associated with gender， age， tumor site， the depth of tumor invasion and clinical TNM stages， but with differentiation grades and lymph node metastasis（P＜0.05）.There was a negative correlation between Skp2 and p27 expression（r=-0.750，P＜0.001）. Conclusion Skp2 and p27 expression involve in the development and progression from normal esophageal tissue to esophageal carcinoma，and may be correlated to the onset and progress of esophageal carcinoma.

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Expression of Fn14 in esophageal squamous cell carcinoma and its clinical significance

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

Chinese Clinical Oncology. 2015, 7 (7): 620.

Abstract ( 763 )

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Objective To investigate the expression of fibroblast growth factor-inducible 14（Fn14）in esophageal carcinoma and its relationship with clinical data and prognosis of patients with esophageal squamous cell carcinoma（ESCC）. Methods In this study， Fn14 expression in tumor tissues was assessed using immunohistochemical（IHC）methods in 118 patients with resected ESCC. The association of Fn14 expression with clinicopathological parameters were also evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of Fn14 expression on survival. Results It showed that Fn14 was expressed in 51.7% （61/118） and 4.2% （5/118） of cancer lesions and corresponding adjacent non-cancerous tissue， respectively （P＜0.001）. Fn14 expression was significantly correlated with lymphatic metastasis and TNM stage（P＜0.001）. The median overall survival of Fn14 positive expression patients and negative expression patients were 23 months（95%CI：17-29 months） and 54 months（95%CI：50-58 months） with statistical significance （P＜0.001）. Multivariate analysis indicated that in addition to the T and N stage， Fn14 expression may also be an independent prognostic factor in ESCC （HR=1.51， 95%CI：1.02-2.24， P=0.022）. Conclusion Fn14 expression is of clinical significance and can serve as a prognostic biomarker in ESCC.

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Relationship between the expression of PD-1 on CD8+T cell and the clinical pathological parameters in non-small cell lung cancer

ZHOU Li， REN Fang， ZHANG Guannan， LV Xiying.

Chinese Clinical Oncology. 2015, 7 (7): 625.

Abstract ( 761 )

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Objective To explore the expression characteristics of programmed death-1（PD-1） on CD8+T in the peripheral blood from patients with non-small cell lung cancer （NSCLC） as well as the relationship between level of PD-1 and clinicopathologic variables. Methods Ninety NSCLC patients， including 50 squamous cell carcinoma and 40 adenocarcinoma， and thirty healthy controls were selected. CD8+T cells were obtained from the peripheral blood mononuclear cells. The positive expression ratio of the PD-1 on the CD8+T cell surfaces in the peripheral blood was detected using flow cytometry. We then analyzed the relationship of PD-1 expression with age， gender， pathological classification， clinical stage， pathological degree and lymphatic metastasis. Results The positive expression ratio of PD-1 on CD8+T cell in the peripheral blood of the three groups were （18.32±5.20）%，（18.68±5.41）% and （7.44±2.59）%， and the data of NSCLC patients was higher than that of the healthy controls （F=58.344， P＜0.001）.The results were obviously related to the clinical stage and lymphatic metastasis （P＜0.05）， which positively correlated with the clinical stage of the NSCLC （rs=0.875， P＜0.001）. However， no difference was observed on age， gender， pathological classification and pathological degree （P＞0.05）. Conclusion The positive expression ratio of PD-1 on CD8+T cell in the peripheral blood of NSCLC patients was higher than that of the healthy controls， and the high expression ratio of PD-1 on CD8+T cell were significantly related to the clinical stages and lymphatic metastasis. The elevated level of PD-1 might be related with the immune escape of the NSCLC， thus playing a crucial role in the occurrence and development of NSCLC.

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Clinical observation on gemcitabine combined with xeloda and calcium folinate tablets as the first-line regimen for advanced billiary tract carcinoma

LI Rong， QIN Shukui，LIU Xiufeng，WANG Lin，HUA Haiqing，CHEN Yingxia.

Chinese Clinical Oncology. 2015, 7 (7): 629.

Abstract ( 860 )

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Objective To observe the efficacy and safety of gemcitabine combined with xeloda and calcium folinate tablets（GLX） as the first-line regimen for advanced billiary tract cancers（BTCs）. Methods From April 2008 to October 2014，48 patients diagnosed as BTCs by pathologic and imaging examination were treated with GLX as the first-line regimen. Gemcitabine was administrated intravenously at the dose of 1000 mg/m2 for about 30 min on d1 and d8， and Xeloda 1250 mg/m2 and calcium folinate tablets 40-60 mg/m2 twice daily， oral application d1-d14. Regimen was repeated every 3 weeks. The efficacy was evaluated strictly after 2 cycles according to RECIST 1.1 criteria， and quality of life （QoL）was evaluated accoding to karnofsky scores. Side effects was evaluated after 1 cycle according to NCI-CTC 4.0 version criteria. The patients were followed-up for the time to progression （TTP） and overall survival （OS）. Results All patients received 238 cycles totally and mean cylces was 4.9 ranged from 2 to 10. All were eligible for efficacy and toxicity evaluation. There were 1 case of CR, 8 PR and 26 SD. The overall response rate was 18.7% and disease control rate was 72.9%. The medium TTP was 7 months and the medium OS was 13 months. The quality of life（QoL） were improve on 23 cases，stabled on 15 cases and decreased on 10 case with the effective rate of 72.9%. Most common toxicity in grade 3 were leucopenia（6.3%） and hand-foot syndrome （6.3%）. Conclusion GLX as first-line treatment of advanced metastatic BTCs has good effect， and may improve or stabilize the patients QoL with longer TTP and OS. GLX regimen is well tolerated， which is worthy of clinical use and further observation.

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Therapeutic effect and safety of combined bevacizumab with chemotherapy in previously treated advanced patients with non-small cell lung cancer

ZHENG Jingxian， ZHANG Jing， LIN Jing， XU Zhenwu， WU Biao， ZHU Kai， HUANG Cheng.

Chinese Clinical Oncology. 2015, 7 (7): 633.

Abstract ( 784 )

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Objective To explore the therapeutic effect and safety of bevacizumab combined with chemotherapy in previously treated advanced patients with non-small cell lung cancer （NSCLC）.
Methods In this study， 84 patients pathologically in accordance with the feature of advanced NSCLC were treated with bevacizumab combined with chemotherapy from May 2010 to July 2014. The curative effect was analyzed according to Response Evaluation Criteria in Solid Tumors （RECIST） 1.1 every 2 cycles. The National Cancer Institute Common Toxicity Criteria （NCI-CTC） version 3.0 was employed to evaluate the adverse reaction. Survival analysis was performed using Kaplan-Meier method. Results All the 84 patients were evaluable for response. There were no CR cases， 12 cases of PR， 42 cases of SD and 30 cases of PD with the response rate and disease control rate of 14.8% and 64.8%. The median progression free survival and overall survival were 3.8 months and 8.8 months， respectively. The main adverse reactions of bevacizumab were hypertension， bone marrow suppression, liver function damage and skin rash， manifested most as degree 1-2 but rarely degree 3-4. Conclusion It was effective and safe for advanced NSCLC patients treated with bevacizumab combined with chemotherapy.

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Clinicopathological characteristics of 110 interval cancer cases in breast cancer screening

LI Yi， LV Yanli， ZHAO Yue， QIN Hongfeng， YANG Chunxia， ZHANG Jianhua.

Chinese Clinical Oncology. 2015, 7 (7): 637.

Abstract ( 702 )

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Objective To explore the clinical and pathological characteristics of 110 interval cancer cases in first three rounds breast cancer screening of Shunyi District. Methods The breast cancer incidence registration system and the database of breast cancer screening were linked to identify the interval cancer cases. The characteristics of interval breast cancers were compared with breast cancers from the outpatients among the same period. Results Compared with breast cancer outpatients， interval cancer cases were younger and of smaller size on breast ultrasonography（P＜0.05）. Compared with similar size of breast cancer outpatients， true interval cancer cases had significantly higher proportions of malignant calcification on mammography and invasive ductal carcinoma（P＜0.05）. Among the total 110 interval breast cancer cases， only 1 case was assigned to mammography as a referral， and the referral proportion was only 0.91%. In regard to the diagnosis mammography， 53 out of 103 interval cases（48.2%） were characterized by malignant calcification. Conclusion In breast cancer screening， women with younger age are prone to interval cancer. As nearly half of the interval cancer cases contained malignant calcification on diagnostic mammography， breast cancer screening using breast ultrasonography and additional mammography may avoid part of interval cancer cases.

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Clinical observation of EGFR-TKIs for the novel histological subtypes of lung adenocarcinoma with EGFR mutation

CAI Zhongfu， YU Zongyang， OUYANG Xuenong， ZHANG Yan， ZHANG Jiangling.

Chinese Clinical Oncology. 2015, 7 (7): 642.

Abstract ( 740 )

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Objective To investigate the relationship between histological subtypes and the efficacy of epidermal growth factor receptor tyrosine kinase inhixitors（EGFR-TKIs） based on EGFR mutation. Methods Eighty-three cases of EGFR mutations-positive advanced lung adenocarcinoma received the EGFR-TKIs treatment form Jun 1，2009 to Dec 30，2012 from Fuzhou General Hospital of Nanjing Military Region and its relationship with the efficacy of EGFR-TKIs was reviewed. Reclassification was carried out based on 2011 Lung Adenocarcinoma Classification Standard. EGFR mutation was detected by RT-PCR.According to RECIST 1.1 standards， the efficacy was assessed. Results The total disease control rate （DCR） of 83 patients was 77.1%， including alveolar predominant type 82.9%，solid-predominant type 50%，like spikes type 92.9%，and papillary and micropapillary predominant type 66.6%.Median progression free survival of 83 patients was 16.0 months，including alveolar predominant type 17.0 months，solid predominant type 7.0 months，spikes predominant type 18.0 months，and papillary and micropapillary predominant type 12.0 months. Conclusion Spikes predominant who accepted EGFR-TKIs has a best DCR and PFS，but solid predominant is the worst.Pathological classification is help for predicitng EGFR-TKIs effect.

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Clinicopathological characteristics of mobile spinal chordoma

YANG Yongkun， NIU Xiaohui， LI Lan， DING Yi.

Chinese Clinical Oncology. 2015, 7 (7): 646.

Abstract ( 709 )

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Objective To investigate the clinicopathological characteristics and the methods of diagnosis and treatment of chordoma sites occurred in rare mobile spine. Methods The clinical data of six cases of spinal chordoma occurred in cervical， thoracic and lumbar from December 2001 to December 2013 in our center were analyzed， which including clinical manifestations， radiological features， pathological diagnosis， and surgical treatment. Results There were three cases in lumbar vertebrae， two cases in cervical vertebrae and one case in thoracic vertebrae. All cases received surgical treatment. The average postoperative follow-up time was 38.7（12-45） months. Recurrence occurred in two cases which had intracapsular resection margin. One patient died of multiple metastases postoperative. Pathology showed classic chordoma morphology. Tumor cells showed a patchy distribution or cords and scattered in mucinous abundant interstitial. The tumor was composed of droplets like cells containing vacuole and eosinophilic astrocytes. Conclusion The cervical， thoracic and lumbar spinal chordomas are rare. The clinical symptoms are not typical and easily missed or misdiagnosed. The diagnosis should combine with radiological and pathological characteristic. The recurrence rate is high after intracapsular excision.

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The confirmation of respiratory phase in localization and the correction of Z-axis coordinates under the therapy of gamma knife for hepatic cancer patients

GAO Li， ZHOU Xuan，ZHOU Longxing， LI Shengyuan.

Chinese Clinical Oncology. 2015, 7 (7): 651.

Abstract ( 764 )

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Objective To explore the necessity for the judgement of respiratory phase in localization and the correction of Z-axis coordinates under the therapy of gamma knife for hepatic cancer patients. Methods The motion range of right diaphramatic dome in eupnea and the position of middle point were observed. The position of middle point was marked in body surface using a steel ball with a diameter of 2 mm during CT scan of 5 mm slice thickness. Whether the position of diaphramatic dome and the middle point is in the same slice helped to ascertain the respiratory phase and correct the Z-axis coordinates. Results In the entire 122 patients， there were 38（31%） cases with the position of diaphramatic dome and the middle point in the same slice， 84 cases（69%） not in the same slice，48 cases（39%） with difference of one slice， 18 cases（15%） with difference of two slices， 12 cases（10%） with difference of three slices and 6 cases（5%） with difference of more than three slices. Conclusion The correction of Z-axis and the determination of PTV coordinates should not only refer to the range of respiratory range， but also to the respiratory phase.

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Research progress of cyclin-dependent kinase 4 and 6 in the treatment of breast cancer

YANG Fang， GUAN Xiaoxiang.

Chinese Clinical Oncology. 2015, 7 (7): 654.

Abstract ( 802 )

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Cellular proliferation， growth， and division are tightly controlled by the cell-cycle regulatory machinery. Recently， cyclin-dependent kinase 4 and 6（CDK4/6） inhibitors were identified to be useful in breast cancer patients with positive estrogen receptor or amplified HER-2， whereas the role remains controversial in triple-negative breast cancer. It is of great importance to investigate the predictive biomarkers for identifying which subgroup of breast cancer patients would mostly benefit from such treatment. Moreover， tumor suppressor retinoblastoma（Rb） plays a pivotal importance in breast cancer， and cyclin D-CDK4/6-Rb pathway， governing the cell cycle restriction point in breast cancer， is a potential target for anticancer therapy. In this article, we review the preclinical and clinical data and describe the future development on the role of CDK4/6 inhibitors in breast cancer.

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Research progress of signal transducer and activator of transcription 3 pathway on radiosensitivity of tumor

WANG Kang， BAI Jing.

Chinese Clinical Oncology. 2015, 7 (7): 658.

Abstract ( 743 )

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Studies have shown that signal transducer and activator of transcription 3（STAT3） is over-expressed in many malignant tumors. This signal pathway is closely related to the proliferation， differentiation and apoptosis in tumor cells. The activation of the STAT3 pathway promotes tumor growth and invasion. Emerging studies demonstrated that the abnormal activation of STAT3 resulted in the decrease of tumor radiosensitivity and avoidance of being damaged by radiation. The expression of STAT3 in tumor can be used in evaluating curative effect and prediction of prognosis. Inhibition of STAT3 pathway can markedly reverse the radiotherapy tolerance. The continue research on STAT3 can provide us with more tumor targeting strategies.

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Research progression of Kruppel-like factor 4 in the digestive system neoplasms

TIAN Chuan， LI Qi.

Chinese Clinical Oncology. 2015, 7 (7): 662.

Abstract ( 748 )

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Kruppel-like factor 4（Klf4），a zinc finger-type protein transcription factor，plays an important role in the cell growth， apoptosis， proliferation and differentiation by regulating the expression of a number of downstream target genes. Klf4 is a transcription factor which functions as a tumor suppressor and oncogene. This article summarizes the structure of Klf4， biological function and latest research progress in digestive system neoplasms.

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Hypoxia-inducible factor-1 and cancer stem cells

WANG Wenjing， MEI Mingzhu， QI Cong.

Chinese Clinical Oncology. 2015, 7 (7): 666.

Abstract ( 797 )

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Hypoxia-inducible factor-1（HIF-1） is an oxygen-dependent transcriptional activator produced by cells and tissues under hypoxic conditions. Recent research indicates that HIF-1 is closely related with the generation and maintenance of cancer stem cells（CSCs）. Moreover， HIF-1 can regulate multiple signaling pathways related to CSCs， promote the invasion， metastasis， epithelial mesenchymal transition and angiogenesis of CSCs， enhance tumor resistance and reduce apoptosis under hypoxic conditions. Since HIF-1 is closed related with the generation and development of CSCs， the strategies targeting HIF-1 may play an important role for inhibiting and killing CSCs.

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标准刊号：	ISSN 1009-0460
	CN 32-1577/R