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Chinese Journal of Cancer research 2010年第3期22卷 201-210页

作者： Jian-ping Cheng Ying Yan Xiang-yi Wang Yuan-li Lu Yan-hua Yuan Xiao-li Wang Jun Jia Jun Ren Key Laboratory of Carcinogenesis and Translational research(Ministry of Education) Department of Medical OncologyPeking University School of OncologyBeijing Cancer Hospital&Institute Beijing 100142China

Objective:The purpose of this study is to explore RT-PCR method to set up the examination platform for detecting circulating tumor cells(CTC) in peripheral blood from metastatic breast cancer *** primary endpoint is to find out the correlation of existence of CTC with clinical responses and progression-free survival(PFS).Methods:The breast cancer cell line MCF-7 was serially diluted into the peripheral blood from 45 healthy donors to set up the sensitivity of RT-PCR *** expression of CK19 mRNA was amplified from both 49 patients and 45 healthy donors *** CK19 protein quantity from plasma was measured by competitive inhibition ELISA ***:The sensitivity of RT-PCR could reach 1/106?107 white blood cells with specificity of 95.6%.The objective response rate(ORR) of patients with CK19 mRNA-negative undertaken one cycle chemotherapy was significantly higher than those with positive(P0.0001).PFS among CK19 mRNA-negative patients was also increased,although there was no significance(P=0.098).The results of ELISA assay showed that CK19 protein was decreased significantly after one cycle chemotherapy,which gave rise to a little higher ORR(P=0.015) and increased PFS(P=0.016).Conclusion:Patients with unamplified CK19 mRNA after one cycle chemotherapy could achieve better radiographic evaluation and increased PFS,which was showed to be of consistency with the CK19 protein assay among the patients treated.

关键词： Breast cancer Circulating tumor cells CK19 RT-PCR ELISA

Expression of ΔDNMT3B Variants and Its Association with Estrogen/Progestogen Receptor Status in Breast Cancer

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Chinese Journal of Cancer research 2009年第3期21卷 229-234页

作者： Ning-hong Liu Lu Yang Ming-lei Zhuo Jie Wang Shu-hang Wang Jun Zhao Hua Bai Key Laboratory of Carcinogenesis and Translational research （Ministry of Education） Department of Thoracic Medical Oncology Peking University School of Oncology Beijing Cancer Hospital ＆ Institute Beijing 100142 China

Objective： Our previous study has showed that △DNMT3B is the predominant form of DNMT3B in non-small cell lung cancer （NSCLC）. In this study, we aimed to explore the expression patterns of the △DNMT3B variants in breast cancer and to identify whether the pattern was similar to that in NSCLC or not and its clinical significance. Methods： Expression of seven △DNMT3B variants in 59 breast cancer and the corresponding normal tissue was measured using RT-PCR. The correlations between the expressions of △DNMT3B variants and the clinical parameters including ER/PR status, clincopathologic feature and survivals were analyzed. Results： There were significant differences in the expression ratios of △DNMT3B1-7 variants between breast cancer tissues and normal tissues （P〈0.001）. The positive ratio of △DNMT3B1-7 variants were 66%, 71%, 17%, 51%, 76.2%, 50% and 61% in tumor tissue, respectively; while 16%, 8.4%, 3.38%, 3.38%, 11.8%, 13.5% and 5.08% in the corresponding normal tissue, which was different from the pattern of △DNMT3B1-7 expression in NSCLC （62%, 76%, 2.5%, 46%, 18%, 27% and 16% in tumor tissue, respectively; while 18%, 11%, 0%, 3.3%, 0%, 0% and 0% in normal lung tissue, respectively; P〈0.0001）. Expressions of △DNMT3B2, 3B4 and 3B7 were higher in the patients with negative estrogen receptor （ER） than those with positive estrogen receptor （P=0.035, P=0.0141 and P=0.0219, respectively）. △DNMT3B7 expression was higher for the patients with negative progestogen receptor （PR） compared to those with positive progestogen receptor （P=0.0379）. Expression ratio of △DNMT3B5 in stage Ⅲ tumors is lower than that in stage Ⅰ/Ⅱ ones （P= 0.041）. But we did not find any relation between the △DNMT3B variants and the patients＇ survival. Conclusion： The pattern of △DNMT3B variants in breast cancer is different from that in NSCLC. Expressions of △DNMT3B2, 3B4 and 3B7 are associated with estrogen receptors status. While △DNMT3B7 is associated with progestogen receptor. No relation

关键词： △DNMT3B variants RT-PCR Breast cancer Estrogen receptor Progestogen receptor

Immediate Versus Delayed Treatment with EGFR Tyrosine Kinase Inhibitors after First-line Therapy in Advanced Non-small-cell Lung Cancer

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Chinese Journal of Cancer research 2011年第2期23卷 112-117页

作者： Zhi-jie Wang Tong-tong An Tony Mok Lu Yang Hua Bai Jun Zhao Jian-chun Duan Mei-na Wu Yu-yan Wang Ping-ping Li Hong Sun Ping Yang Jie Wang Key Laboratory of Carcinogenesis and Translational research （Ministry of Education） department of Thoracic medical oncology department of Integrative Medicine Peking University School of Oncology Beijing Cancer Hospital ＆ Institute Beijing China department of Clinical oncology Chinese University of Hong Kong Hong Kong China department of oncology General Hospital of Navy Beijing China

Objective： To analyze the outcomes of patients who received TKI immediately after the first-line without progression as maintenance treatment （immediate group） vs. those received delayed treatment upon disease progression as second-line therapy （delayed group）. Methods： The study included 159 no-small-cell lung cancer （NSCLC） patients who received gefitinib or erlotinib as maintenance treatment in the immediate group （85 patients） or as second-line therapy in the delayed group （74 patients）. The primary end point was progression-free survival （PFS）. EGFR mutation status was detected using denaturing high-performance liquid chromatography （DHPLC）. Results： PFS was 17.3 and 16.4 months in the immediate and delayed groups, respectively （hazard ratio [HR], 0.99; 95% Confidence Interval [CI]： 0.69-1.42; P=0.947）. In a subgroup analysis that included only patients with EGFR mutation, however, PFS was significantly longer in the immediate group than in the delayed group （HR, 0.48; 95% CI： 0.27-0.85; P=0.012）. In patients with wild type EGFR, the risk for disease progression was comparable between the two groups （HR, 1.23; 95% CI： 0.61-2.51; P=0.564）. No significant difference was demonstrated between the immediate and delayed group in terms of the overall survival （OS）（26.1 months vs. 21.6 months, respectively; HR=0.53; 95% CI： 0.27 to 1.06; P=0.072）. There was also no difference in the incidence of adverse events between the two groups. Conclusions： EGFR TKI maintenance improves PFS in patients with EGFR mutation. Prospectively designed clinical studies that compare TKI immediate vs. delayed treatment after first-line chemotherapy upon disease progression are needed.

关键词： EGFR tyrosine kinase inhibitor Maintenance therapy Non-small-cell lung cancer

Expression of VEGFR2 and NRP-1 in non-small cell lung cancer and their clinical significance

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Chinese Journal of Cancer research 2014年第6期26卷 669-677页

作者： Manhua Ding Liang Liu Chengxi Hu Yi Liu Yun Qiao Xiaodong Jiang Xuzhou medical College department of oncology Xuzhou Cancer Hospital department of Radiotherapy oncology Lianyungang First People’s Hospital

Objective： Vascular-targeted therapy is gradually becoming more appealing for patients with lung cancer. It is unclear whether vascular endothelial growth factor receptor 2（VEGFR2） and neuropilin-1（NRP-1） can be biomarkers for clinical treatment. We aimed to investigate the expression levels of VEGFR2 and NRP-1 in human non-small cell lung cancer（NSCLC） and their clinical significance by observing patient prognosis. Methods： VEGFR2 and NRP-1 were assessed by immunohistochemistry（IHC） in 40 patients with NSCLC and in 10 patients with benign lesions of lung; kinase insert domain receptor（KDR） and NRP-1 copy number gain（CNG） was assessed by fluorescence in situ hybridization（FISH）. The distributions of overall survival（OS） and progression-free survival（PFS） were estimated using the Kaplan-Meier method and compared between groups by log-rank ***： Rates of positive immunostaining for VEGFR2 and NRP-1 were 58% and 55%, respectively. KDR and NRP-1 CNG（＋） were detected in 32.5% and 30% of tumors, respectively. Levels of both VEGFR2 and NRP-1 in lung tumors were significantly different than in the control tissue（χ2=11.22, P=0.001; χ2=9.82, P=0.001, respectively）; similar results were obtained using CNGs（χ2=4.39, P=0.036; χ2=3.95, P=0.046, respectively）. Statistically significant correlations were observed with histological grade, clinical TNM stage and the lymph node status（P〈0.05）, but not age, gender or pathology type（P〉0.05）. VEGFR2 showed a strong correlation with NRP-1（Rs=0.68, P=0.00）; similar results were observed with KDR and NRP-1 CNG（Rs=0.32, P=0.04）. Significant differences in OS and PFS were observed between the groups with higher VEGFR2 and NRP-1 and those with lower expression（P〈0.05）. Conclusions： According to these data, VEGFR2 and NRP-1 are highly expressed in NSCLC. We can conclude that they play a key role in NSCLC occurrence, development and metastasis and are associated with patient prognosis（P〈0.05 for OS and PFS）. This information will be bene

关键词： Non-small cell lung cancer(NSCLC) vascular endothelial growth factor receptor 2(VEGFR2) neuropilin-1(NRP-1) fluorescence in situ hybridization(FISH)

Effect of Saikokeishito, a Kampo medicine, on hydrogen peroxide-induced premature senescence of normal human dermal fibroblasts

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Journal of Integrative Medicine 2014年第6期12卷 495-503页

作者： Takanobu Takata Yoshiharu Motoo Naohisa Tomosugi medical research Institute of Kanazawa medical University department of medical oncology Kanazawa Medical University department of Nephrology Kanazawa Medical University

OBJECTIVE： Saikokeishito（TJ-10） is a Kampo（traditional Japanese herbal） medicine, clinically used for hundreds of years in East Asia. Among its various mechanisms elucidated so far, TJ-10 inhibits the production of transforming growth factor-β1（TGF-β1） and development of pancreatic fi brosis in vivo. Oxidative damage of normal human dermal fi broblasts（NHDFs） in the corium is a cause of human dermal senescence. Our aim was to determine whether TJ-10 protects NHDFs from premature senescence by hydrogen peroxide（H2O2）. METHODS： Premature senescence was induced in NHDFs by 200 μmol/L H2O2 for 4 h. Cell viability and the expressions of p53, AMP-activated protein kinase α1（AMPKα1）, AMPKα2, and 14-3-3 protein sigma（14-3-3 σ） were measured in NHDFs treated with TJ-10 for 48 h before exposure to H2O2 for 4 h. RESULTS： Cell viability after treatment with 200 μmol/L H2O2 for 4 h was similar（about 80%） to after pre-treatment with TJ-10. Ascorbic acid as a control did not protect NHDFs from damage by 200 μmol/L H2O2. Treatment with 200 μmol/L H2O2 tended to up-regulate p53 and to down-regulate SIRT1 and AMPKα1, but had no effect on AMPKα2 and 14-3-3 σ expression. Pretreatment with TJ-10 inhibited H2O2-induced up-regulation of p53 and enhanced AMPKα1 expression. CONCLUSION： It is suggested that Saikokeishito has a protective effect on oxidative stressinduced senescence of NHDFs.

关键词： Saikokeishito medicine Kampo premature senescence p53 fibroblasts

Advanced pancreatic ductal adenocarcinoma-Complexities of treatment and emerging therapeutic options

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World Journal of Gastroenterology 2017年第13期23卷 2276-2285页

作者： Chandra Diwakarla Katherine Hannan Nadine Hein Desmond Yip department of medical oncology The Canberra Hospital The John Curtin School of medical research Australian National University ANU medical School Australian National University

Pancreatic ductal adenocarcinoma is a devastating disease with a poor prognosis regardless of stage. To date the mainstay of therapy for advanced disease has been chemotherapy with little incremental im-provements in outcome. Despite extensive research investigating new treatment options the current practices continue to utilise fluorouracil or gemcitabine containing combinations. The need for novel the-rapeutic approaches is mandated by the ongoing poor survival rates associated with this disease. One such approach may include manipulation of ribosome biogenesis and the nucleolar stress response, which has recently been applied to haematological malignancies such as lymphoma and prostate cancer with promising results. This review will focus on the current therapeutic options for pancreatic ductal adenocarcinoma and the complexities associated with developing novel treatments, with a particular emphasis on the role of the nucleolus as a treatment strategy.

关键词： Ribosome biogenesis Nucleolar stress RNA polymerase I Pancreatic ductal adenocarcinoma Chemotherapy

Management of extramedullary plasmacytoma: Role of radiotherapy and prognostic factor analysis in 55 patients

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Chinese Journal of Cancer research 2017年第5期29卷 438-446页

作者： Ge Wen Weihu Wang Yujing Zhang Shaoqing Niu Qiwen Li Yexiong Li Key Laboratory of Carcinogenesis and Translational research (Ministry of Education/Beijing) Department of Radiation Oncology Peking University Cancer Hospital & Institute department of Radiation oncology the Third Affiliated Hospital of Guangzhou Medical University department of Radiation oncology Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center of Cancer Medicine department of Radiation oncology the First Affiliated Hospital of Sun Yat-sen University department of Radiation oncology National Cancer Center/Cancer Hospital Chinese Academy of Medical Science & Peking Union Medical College

Objective： To investigate potential prognostic factors affecting patient outcomes and to evaluate the optimal methods and effects of radiotherapy（RT） in the management of extramedullary plasmacytoma（EMP）.Methods： Data from 55 patients with EMP between November 1999 and August 2015 were collected. The median age was 51（range, 22–77） years. The median tumor size was 3.5（range, 1.0–15.0） cm. The median applied dose was 50.0（range, 30.0–70.0） Gy. Thirty-nine patients（70.9%） presented with disease in the head or neck region. Twelve patients received RT alone, 9 received surgery（S） alone, 3 received chemotherapy（CT） alone, and 3 patients did not receive any treatment. Combination therapies were applied in 28 ***：The median follow-up duration was 56 *** 5-year local recurrence-free survival（LRFS）,multiple myeloma-free survival（MMFS）,progression-free survival（PFS）and overall survival（OS）rates were 79.8%,78.6%,65.2% and 76.0%,*** analysis revealed that RT was a favourable factor for all examined ***,head and neck EMPs were associated with superior LRFS,MMFS and *** size〈4 cm was associated with superior MMFS,PFS and OS;serum M protein negativity was associated with superior MMFS and PFS;age≥50 years and local recurrence were associated with poor *** dose≥45 Gy group exhibited superior 5-year LRFS,MMFS and PFS rates（94.7%,94.4%,90.0%,respectively）,while the corresponding values for the dose〈45 Gy group were 62.5%（P=0.008）,53.3%（P=0.036）and 41.7%（P〈0.001）.Conclusions：Involved-site RT of at least 45 Gy should be considered for ***,patients with head and neck EMP,tumor size〈4 cm,age〈50 years and serum M protein negativity had better outcomes.

关键词： Extramedullary plasmacytoma prognostic factors radiotherapy multiple myeloma

Prognostic Factors for Patients after Curative Resection for Proximal Gastric Cancer

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Journal of Huazhong University of Science and Technology(medical Sciences) 2010年第4期30卷 530-535页

作者：赵东晖徐惠绵李凯孙哲 department of Surgical oncology Research Unit of General Surgery Department of Gastrointestinal Oncosurgery First Affiliated Hospital of China Medical University

The factors influencing the long-term survival of patients with proximal gastric cancer (PGC) after curative resection were investigated. Data from 171 patients who underwent curative resection for PGC were retrospectively analyzed. The patients were grouped according to the clinicopathological factors and operative procedures. The tumor depth (T stage) and lymph node metastasis (pN stage) were graded according to the fifth edition of TNM Staging System published by UICC in 1997. The metastatic lymph node ratio (MLR) was divided into four levels: 0%, 30%. The data of survival rate were analyzed by Kaplan-Meier method (log-rank test) and Cox regression model. The 5-year overall survival rate of 171 patients was 37.32%. The univariate analysis demonstrated that the survival time of the postoperative patients with PGC was related to tumor size (χ2=4.57, P=0.0325), gross type (χ2=21.38, P30% (χ2=13.34, P=0.0003), TNM Ⅲ (χ2=14.05, P=0.0002) or TNM Ⅳ stage (χ2=4.37, P=0.0366); and combining splenectomy was beneficial to the cases of T3 (χ2=5.68, P=0.0171) or MLR >30% (χ2=6.11, P=0.0134). It was concluded that MLR, pN stage, TNM stage, T stage, and gross type had advantages in providing a precise prognostic evaluation for patients undergoing curative resection for PGC, in which MLR was the most valuable index. TG and combining splenectomy were useful to improve the prognosis to patients with PGC of TNM Ⅲ/Ⅲ stage, serosa invasion, or extensive regional lymph node metastasis.

关键词： stomach neoplasms proximal gastric cancer curative resection prognosis.

Change of SPARC expression after chemotherapy in gastric cancer

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Cancer Biology & Medicine 2015年第1期12卷 33-40页

作者： Yong-Yin Gao Ru-Bing Han Xia Wang Shao-Hua Ge Hong-Li Li Ting Deng Rui Liu Ming Bai Li-Kun Zhou Xin-Yuan Zhang Yi Ba Ding-Zhi Huang department of Gastrointestinal medical oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and Therapy

Objective： The expression of tumor biomarkers may change after chemotherapy. However, whether secreted protein acidic and rich in cysteine （SPARC） expression changes after chemotherapy in gastric cancer （GC） is unclear, qqais study investigated the influence of chemotherapy on SPARC expression in GC. Methods： Immunohistochemistry was used to analyze SPARC expression in 132 GC cases （including 54 cases with preoperative chemotherapy and 78 cases without preoperative chemotherapy）. SPARC expression of postoperative specimens with and without preoperative chemotherapy was assessed to analyze the influence of chemotherapy on SPARC expression. Results： SPARC was highly expressed in GC compared with the desmoplastic stroma surrounding tumor cells and noncancerous tissues. High SPAKC expression was correlated with invasion depth, lymph node, and TNM stage. After chemotherapy, a lower proportion of high SPARC expression was observed in patients with preoperative chemotherapy than in the controls. For 54 patients with preoperative chemotherapy; gross type, histology, depth of invasion, lymph node, TNM stage, and SPARC expression were related to overall survival. Further multivariate analysis showed that lymph node, histology, and SPARC expression after chemotherapy were independent prognostic factors. Conclusiou： SPARC expression may change after chemotherapy in GC. SPARC expression should be reassessed for patients with GC after chemotherapy.

关键词： Secreted protein acidic and rich in cysteine (SPARC) gastric cancer (GC) immunohistochemistry chemotherapy

Right-sided colon cancer and left-sided colorectal cancer respond differently to cetuximab

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癌症 2015年第9期34卷 384-393页

作者： Feng Wang Long Bai Tian-Shu Liu Yi-Yi Yu Ming-Ming He Kai-Yan Liu Hui-Yan Luo Dong-Sheng Zhang Yin Jin Feng-Hua Wang Zhi-Qiang Wang De-Shen Wang Miao-Zhen Qiu Chao Ren Yu-Hong Li Rui-Hua Xu department of medical oncology Sun Yat-sen University Cancer Center:State Key Laboratory of Oncology in South China department of medical oncology Zhongshan HospitalFudan University Collaborative Innovation Center for Cancer Medicine

Introduction: Right-sided colon cancer(RSCC) and left-sided colorectal cancer(LSCRC) differ with respect to their biology and genomic patterns. This study aimed to examine whether the primary tumor location is associated with the response to cetuximab in patients with metastatic colorectal cancer(m CRC).Methods: Patients with mC RC treated with cetuximab and standard chemotherapy as first- or second-line treatments were compared with randomly chosen patients who were treated with chemotherapy alone between 2005 and *** main outcome measures were the overal response rate(ORR), progression-free survival(PFS), and overal survival(OS).The differences in the outcome were analyzed by using the chi-squared test, Student’s t test, and Kaplan-Meier ***: The treatment results of 206 patients with m CRC treated with cetuximab and standard chemotherapy as first- or second-line treatments were compared with those of 210 patients who were treated with chemotherapy alone. As a first-line treatment, cetuximab with chemotherapy was associated with a significantly higher ORR(49.4 % vs. 28.6 %, P = 0.005) as well as longer PFS(9.1 vs. 6.2 months, P = 0.002) and OS(28.9 vs. 20.1 months,P = 0.036) than chemotherapy alone in patients with LSCRC. However, cetuximab neither improved the ORR(36.4 % vs. 26.2 %, P = 0.349) nor prolonged PFS(5.6 vs. 5.7 months, P = 0.904) or OS(25.1 vs. 19.8 months, P = 0.553) in patients with RSCC. As a second-line treatment, cetuximab exhibited a tendency to improve the ORR(23.5 % vs. 10.2 %,P = 0.087) and prolong PFS(4.9 vs. 3.5 months, P = 0.064), and it significantly prolonged OS(17.1 vs. 12.4 months,P = 0.047) compared with chemotherapy alone in the patients with LSCRC. In contrast, as a second-line treatment,cetuximab neither improved the ORR(7.1 % vs. 11.4 %, P = 0.698) nor prolonged PFS(3.3 vs. 4.2 months, P = 0.761) or OS(13.4 vs. 13.0 months, P = 0.652) in patients with ***: The addition of cetuximab to chemotherapy in b

关键词： Colorectal neoplasms Cetuximab Left-sided Right-sided Chemotherapy