You Lu

Publications of You Lu

• [Detection of epidermal growth factor receptor gene mutation in non-small cell lung cancer by allele-specific oligonucleotide-PCR and bi-loop probe specific primer quantitative PCR].

  Authors: Lei Deng, Yuan Tang, Jing Lin, Xiao-jun Lu, Jian-xin Xue, Li-shuai Wang, Lin Zhou, Yan Zou, Bin-wu Ying, Gan-di Li, You Lu

  Zhonghua bing li xue za zhi Chinese journal of pathology. 01/2012; 41(1):20-2.

  To compare the detection sensitivity of epidermal growth factor receptor (EGFR) mutations between allele specific oligonucleotide PCR (ASO-PCR) and bi-loop probe and specific primer quantitative PCRTo compare the detection sensitivity of epidermal growth factor receptor (EGFR) mutations between allele specific oligonucleotide PCR (ASO-PCR) and bi-loop probe and specific primer quantitative PCR (BPSP-qPCR). A total of 96 non-small cell lung cancer specimens were selected from West China Hospital from September 2009 to December 2010. ASO-PCR was developed to detect the presence of classical EGFR mutations. A total 39 available specimens were also tested by BPSP-qPCR. EGFR mutation detection rate was 30.2% (26/96) by ASO-PCR. The mutation rate was higher in female than in male patients [45.5% (20/44) vs. 17.3% (9/52), P = 0.003], non-smokers than smokers [44.1% (26/59) vs. 8.1% (3/37), P < 0.001] and adenocarcinomas than other subtypes of lung cancer [37.0% (27/73) vs. 8.7% (2/23), P = 0.01]. Among mutation negative cases by ASO-PCR, BPSP-qPCR increased the rate of detection of 19-del and L858R mutation by 10.3% (4/39) in adenocarcinomas and non-smoking subset. Overall, the mutation detection rate of BPSP-qPCR was higher than that of ASO-PCR [66.7% (26/39) vs. 41.0% (16/39), P = 0.02]. BPSP-qPCR has a better detection sensitivity than that of ASO-PCR.

• [Detection of epidermal growth factor receptor gene mutations in non-small cell lung cancer using bi-loop probe specific primer quantitative PCR].

  Authors: Li-shuai Wang, Yu Zhang, Xiao-jun Lu, Hua-jun Lu, Lin Zhou, Yong-sheng Wang, Lei Deng, Mei-juan Huang, Feng Peng, Jin Wang, Li Ren, Mei Hou, Lu Li, Yong Xu, Bin-wu Ying, You Lu

  Zhonghua bing li xue za zhi Chinese journal of pathology. 10/2011; 40(10):667-70.

  To investigate the sensitivity of bi-loop probe and specific primer quantitative PCR (BPSP-qPCR) in the detection of epidermal growth factor receptor (EGFR) gene mutations in non-small cell lungTo investigate the sensitivity of bi-loop probe and specific primer quantitative PCR (BPSP-qPCR) in the detection of epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer (NSCLC). BPSP-qPCR was employed to examine the presence of mutations of EFGR exon 19 through 21. Correlation of the mutations with clinicopathological characteristics and types of tumor samples were performed. In the cohort of 265 specimens, 30.2% (80/265) mutations were found to be 19-del and/or L858R. Females (39.7%, 31/78), non-smokers (41.0%, 43/105) and adenocarcinoma patients (37.8%, 51/135) had a higher mutation rate (P<0.05) among 184 patients whose profiles were available. T790M combined with 19-del and/or L858R accounted for 3.3% (6/184) of the mutations. Male metastatic tumors (29.6%, 8/27), pleural fluids of females (42.9%, 9/21) and non-smokers (40.7%, 11/27) were found to have higher percentage of 19-del and/or L858R mutations, in contrast, no mutations were found in the metastatic lesions of non-adenocarcinoma patients (P>0.05). BPSP-qPCR is a robust method in detection of EGFR mutations with high consistency and sensitivity. The difference of EGFR mutations in primary tumors, metastatic lesions and pleural fluids suggests that EGFR tyrosine kinase inhibitors (EGFR-TKI) treatment may have variable treatment effects depending on the tumor sites.

• Clinical management of gastric cancer: results of a multicentre survey.

  Authors: Xiaolong Zhang, Nanjing Li, Wen Wei, Wenxiu Yao, Ke Xie, Jiankun Hu, Lida Shen, Weizheng Ji, You Lu, Feng Wen, Yu Jiang, Feng Xu, Hong Feng, Feng Bi, Qiu Li

  BMC cancer. 08/2011; 11:369.

  ABSTRACT: The National Comprehensive Cancer Network clinical practice guidelines in oncology-gastric cancer guidelines have been widely used to provide appropriate recommendations for the treatmentABSTRACT: The National Comprehensive Cancer Network clinical practice guidelines in oncology-gastric cancer guidelines have been widely used to provide appropriate recommendations for the treatment of patients with gastric cancer. The aim of this study was to examine the adherence of surgical oncologists, medical oncologists, and radiation oncologists' to the recommended guidelines. A questionnaire asking the treatment options for gastric cancer cases was sent to 394 Chinese oncology specialists, including surgical oncologists, medical oncologists, and radiation oncologists working in hospitals joined in The Western Cooperative Gastrointestinal Oncology Group of China. The questionnaire involved a series of clinical scenarios regarding the interpretation of surgery, neoadjuvant, adjuvant, and advanced treatment planning of gastric cancer. Analysis of 358 respondents (91%) showed variations between each specialization and from the recommended guidelines in the management approaches to specific clinical scenarios. The majority of specialists admitted that less than 50% of patients received multidisciplinary evaluation before treatment. The participants gave different responses to questions involving adjuvant, neoadjuvant, and advanced settings, compared to the recommended guidelines. These results highlight the heterogeneity of the treatment of gastric cancer. Surgical oncologists, medical oncologists, and radiation oncologists are not adhering to the recommended guidelines.

• Blockade of lysophosphatidic acid receptors LPAR1/3 ameliorates lung fibrosis induced by irradiation.

  Authors: Lu Gan, Jian-Xin Xue, Xin Li, De-Song Liu, Yan Ge, Pei-Yan Ni, Lin Deng, You Lu, Wei Jiang

  Biochemical and biophysical research communications. 05/2011; 409(1):7-13.

  Lung fibrosis is a common and serious complication of radiation therapy for lung cancer, for which there are no efficient treatments. Emerging evidence indicates that lysophosphatidic acid (LPA) andLung fibrosis is a common and serious complication of radiation therapy for lung cancer, for which there are no efficient treatments. Emerging evidence indicates that lysophosphatidic acid (LPA) and its receptors (LPARs) are involved in the pathogenesis of fibrosis. Here, we reported that thoracic radiation with 16Gy in mice induced development of radiation lung fibrosis (RLF) accompanied by obvious increases in LPA release and LPAR1 and LPAR3 (LPAR1/3) transcripts. RLF was significantly alleviated in mice treated with the dual LPAR1/3 antagonist, VPC12249. VPC12249 administration effectively prolonged animal survival, restored lung structure, inhibited fibroblast accumulation and reduced collagen deposition. Moreover, profibrotic cytokines in radiation-challenged lungs obviously decreased following administration of VPC12249, including transforming growth factor β1 (TGFβ1) and connective tissue growth factor (CTGF). In vitro, LPA induced both fibroblast proliferation and CTGF expression in a dose-dependent manner, and both were suppressed by blockade of LPAR1/3. The pro-proliferative activity of LPA on fibroblasts was inhibited by siRNA directed against CTGF. Together, our data suggest that the LPA-LPAR1/3 signaling system is involved in the development of RLF through promoting fibroblast proliferation in a CTGF-dependent manner. The LPA-LPAR1/3-CTGF pathway may be a potential target for RLF therapy.

• Impacts of multileaf collimators leaf width on intensity-modulated radiotherapy planning for nasopharyngeal carcinoma: analysis of two commercial elekta devices.

  Authors: Shichao Wang, Youling Gong, Qingfeng Xu, Sen Bai, You Lu, Qingfeng Jiang, Nianyong Chen

  Medical dosimetry : official journal of the American Association of Medical Dosimetrists. 01/2011; 36(2):153-9.

  We compared the impacts of multileaf collimator (MLC) widths (standard MLC width of 10 mm [SMLC] and micro-MLC width of 4 mm [MMLC]) on intensity-modulated radiotherapy (IMRT) planning forWe compared the impacts of multileaf collimator (MLC) widths (standard MLC width of 10 mm [SMLC] and micro-MLC width of 4 mm [MMLC]) on intensity-modulated radiotherapy (IMRT) planning for nasopharyngeal carcinoma (NPC). Ten patients with NPC were recruited in this study. In each patient's case, plans were generated with the same machine setup parameter and optimizing methods in a treatment planning system according to 2 commercial Elekta MLC devices. All of the parameters were collected from dose-volume histograms of paired plans and evaluated. The average conformity index (CI) and homogeneous index (HI) for the planning gross target volume in IMRT plans with MMLC were 0.790 ± 0.036 and 1.062 ± 0.011, respectively. Data in plans with SMLC were 0.754 ± 0.038 and 1.070 ± 0.010, respectively. The differences were statistically significant (p < 0.05). Compared with CI and HI for planning target volume in paired plans, data with MMLC obviously were better than those with SMLC (CI: 0.858 ± 0.026 vs. 0.850 ± 0.021, p < 0.05; and HI: 1.185 ± 0.011 vs. 1.195 ± 0.011, p < 0.05). However, there was no statistical significance between evaluated parameters (Dmean, Dmax, D₅, gEUD, or NTCP) for organs at risk (OARs) in the 2 paired IMRT plans. According to these two kinds of Elekta MLC devices, IMRT plans with the MMLC have significant advantages in dose coverage for the targets, with more efficiency in treatment for NPC but fail to improve dose sparing of the OARs.

• Effects of lysophosphatidic acid and its receptors LPA⅓ on radiation pneumonitis.

  Authors: Jianxin Xue, Lu Gan, Xin Li, Jian Li, Guohai Qi, Yalan Wu, Xiaoyue Fu, Qing Mao, Rui Ao, Jingyi Lang, You Lu

  Oncology reports. 12/2010; 24(6):1515-20.

  Radiation pneumonitis (RP) is a serious complication of radiation therapy for thoracic tumors. Lysophosphatidic acid (LPA) and its receptors LPA⅓ were reported to participate in the processes ofRadiation pneumonitis (RP) is a serious complication of radiation therapy for thoracic tumors. Lysophosphatidic acid (LPA) and its receptors LPA⅓ were reported to participate in the processes of inflammation. We tested the hypothesis that LPA and its receptors LPA⅓, take part in the pathogenesis of RP. In our study, irradiation increased LPA levels in the lung and expression of LPA⅓. To further determine the role of LPA⅓, we performed pharmacological knockout of LPA⅓ by a specific antagonist, VPC-12249. On day 60 post-irradiation, RP was significantly alleviated in a dose-dependent manner in mice treated with VPC-12249, as shown by H&E staining, malondialdehyde (MDA, an indicator of oxidative damage) assay in lung, and concentrations of proinflammatory and profibrotic cytokines in plasma, including IL-1β, TNF-α, and TGF-β1. Additionally, VPC-12249 administration decreased the phosphorylation of IκB-α (the initial event that activates the NF-κB signal way), and expression of TGF-β1, CTGF, and α-SMA mRNA. Our findings suggest that LPA and LPA⅓ may play a pivotal role in RP, and LPA-LPA⅓ may serve as novel therapeutic targets for the treatment of RP.

• [Current situation and prospect of treatment for radiation-induced lung injury].

  Authors: Xin Li, Jianxin Xue, You Lu

  Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi. 08/2010; 27(4):937-40.

  Radiation-induced lung injury (RILI) is the most common complication of the radiotherapy for thoracic tumor. It can lower the ratio of local control and seriously affect the patients' quality ofRadiation-induced lung injury (RILI) is the most common complication of the radiotherapy for thoracic tumor. It can lower the ratio of local control and seriously affect the patients' quality of life. At present, the clinical management of RILI is not more than the use of glucocorticoid and anti-inflammatory agent for symptomatic treatments. These treatments do not have any preventive effect but cause much side reactions. In this paper, we review the data from the contigency researches on the mechanism of RILI, from the researches on gene therapy and stem cell-therapy, and we dicuss the more safe, more stable and more efficacious treatment of RILI.

• Evaluation of positioning accuracy of four different immobilizations using cone-beam CT in radiotherapy of non-small-cell lung cancer.

  Authors: Jin Wang, Renming Zhong, Sen Bai, You Lu, Qingfeng Xu, Xiao-Juan Zhou, Feng Xu

  International journal of radiation oncology, biology, physics. 07/2010; 77(4):1274-81.

  To evaluate the positioning accuracy of four different immobilizations by use of cone-beam computed tomography guidance for radiotherapy of non-small-cell lung cancer (NSCLC). Sixty-seven patientsTo evaluate the positioning accuracy of four different immobilizations by use of cone-beam computed tomography guidance for radiotherapy of non-small-cell lung cancer (NSCLC). Sixty-seven patients with NSCLC received conventional or stereotactic body radiotherapy. Of these, 30 were immobilized with a thermoplastic frame (TF), 16 with a thermoplastic frame and active breathing control (TF-ABC), 7 with a stereotactic body frame (SBF), and 14 with a stereotactic body frame and active breathing control (SBF-ABC). Cone-beam computed tomography scans at initial setup and after correction were registered to planning computed tomography. The positional errors in the left-to-right, superior-inferior, and anterior-posterior directions were analyzed. The planning target volume margins were calculated. The precorrection systematic and random errors ranged from 1.9 to 4.2 mm for TF, 1.9 to 4.3 mm for SBF, 1.2 to 5.8 mm for TF-ABC, and 2.3 to 3.9 mm for SBF-ABC. The postcorrection systematic and random errors ranged from 0.3 to 1.9 mm for the four immobilizations. The planning target volume margins (conventional vs. stereotactic body radiotherapy) were 15.6 vs. 13.9 mm (TF), 14.9 vs. 14.8 mm (TF-ABC), 14.4 vs. 13.4 mm (SBF), and 9.9 vs. 9.4 mm (SBF-ABC) before correction and 7.3 vs. 6.9 mm (TF), 4.0 vs. 3.8 mm (TF-ABC), 7.5 vs. 7.1 mm (SBF), and 4.5 vs. 4.2 mm (SBF-ABC) after correction. The positioning accuracies of SBF and TF were similar. Active breathing control increased positioning error but reduced internal margin. Cone-beam computed tomography online correction improved the positioning accuracy of NSCLC patients.

• Effects of heterochromatin in colorectal cancer stem cells on radiosensitivity.

  Authors: Ting Chen, Yu Zhang, Wen-Hao Guo, Mao-Bin Meng, Xian-Ming Mo, You Lu

  Chinese journal of cancer. 03/2010; 29(3):270-6.

  Radiotherapy (RT) is a major non-surgical modality in the comprehensive treatment for colorectal adenocarcinoma. The radioresistance of cancer stem cells (CSCs) is a key factor that influencesRadiotherapy (RT) is a major non-surgical modality in the comprehensive treatment for colorectal adenocarcinoma. The radioresistance of cancer stem cells (CSCs) is a key factor that influences therapeutic effectiveness. This study was to investigate the effects of specific chromosome structure and histone modification in CSCs in colorectal adenocarcinoma radioresistance. Samples were collected from resected human colorectal adenocarcinomas. Subcutaneous colorectal cancer model was established in nude mice. Immunohistochemistry showed that xenografts generated from bulk colorectal cancer cells resembled the original tumor specimen. Flow cytometry was performed to sort CSCs (CD133+) and non-CSCs (CD133-) from both resected samples of colorectal adenocarcinoma and xenograft before and after high single-dose radiation. The markers labeling heterochromatin (H3K9me3, HP1-alpha and H3K4me1) and euchromatin (H3K4me3) in CD133+ and CD133- nucleus were detected by immunofluorescence. There was distinct difference in chromatin structure between colorectal CSCs (CD133+) and non-CSCs (CD133-). The chromatin displayed compact patches in CD133+ nucleus, but loosely latticed structure in CD133- nucleus; immunofluorescence verified that the compact patches existing in CSCs was generated from heterochromatin construction. In addition, the vacuole-like defect in heterochromatin regions of CSCs was observed within 24 h after exposure to 10 gray (Gy) single-dose RT. Interestingly, this phenomenon was repaired from 96 h, and recovered to dense plaque structure in heterochromatin regions of CSCs after 144 h. However, no significant difference in non-CSCs was observed after RT exception for a loose chromatin structure. CSCs play a role in radiosensitivity in colorectal cancer. The mechanism may be related to heterochromatin formation and histone methylation.

• A phase I clinical and pharmacokinetic study of paclitaxel liposome infused in non-small cell lung cancer patients with malignant pleural effusions.

  Authors: Xianhuo Wang, Junchao Zhou, Yongsheng Wang, Zhengyan Zhu, You Lu, Yuqan Wei, Lijuan Chen

  European journal of cancer (Oxford, England : 1990). 03/2010; 46(8):1474-80.

  To investigate the feasibility, pharmacokinetics, efficacy and toxicity of intrapleural paclitaxel liposome injection in non-small cell lung cancer (NSCLC) patients with malignant pleuralTo investigate the feasibility, pharmacokinetics, efficacy and toxicity of intrapleural paclitaxel liposome injection in non-small cell lung cancer (NSCLC) patients with malignant pleural effusions. Twelve of 15 NSCLC patients with malignant pleural effusions were treated with paclitaxel liposome and three were treated with free paclitaxel. Adequate pleural fluid, blood and urine were collected for pharmacokinetic study. The clinical efficacy and toxicity were synthetically evaluated according to the correlative criteria. The overall toxicity of paclitaxel liposome was lower than that of free paclitaxel. In the patients treated with paclitaxel liposome, there were minimal local chest pain, anaphylaxis, anaemia, neutropaenia and hepatotoxicity. The complete response rates of pleural effusion at the first, second, third and sixth month were, respectively, 27.3%, 18.2%, 9.1% and 9.1%, and overall response rates were 90.9%, 72.7%, 63.6% and 54.5%, respectively. Pharmacokinetic study showed that mean C(max,IP), T(1/2) and AUC(0-->96,IP) in pleural fluid were, respectively, about 2-fold, 2-fold and 2.5-fold than those of free paclitaxel, and AUC(0-->96,Pla) in plasma was also much higher than that of free paclitaxel, however, excretory rate in 24h from urine was lower than that of free paclitaxel. This study demonstrated that paclitaxel liposome was a more useful agent than free paclitaxel for the treatment of malignant pleural effusions because of its relatively low toxicity and distinct pharmacokinetic characteristics. The phase II study of a large number of patients was recommended to confirm this finding.

• Efficacy of RNAi targeting of pyruvate kinase M2 combined with cisplatin in a lung cancer model.

  Authors: Wenhao Guo, Yu Zhang, Ting Chen, Yongsheng Wang, Jianxin Xue, Yonggang Zhang, Wenjing Xiao, Xianming Mo, You Lu

  Journal of cancer research and clinical oncology. 03/2010; 137(1):65-72.

  Pyruvate kinase isoenzyme M2 (PKM2) is a key enzyme in aerobic glycolysis; inhibition of PKM2 leads to the tumor growth inhibition. In this study, the effects of combined treatment with cisplatinPyruvate kinase isoenzyme M2 (PKM2) is a key enzyme in aerobic glycolysis; inhibition of PKM2 leads to the tumor growth inhibition. In this study, the effects of combined treatment with cisplatin (DDP) and a plasmid that expresses a short hairpin RNA (shRNA) targeting PKM2 on the growth of human A549 xenograft lung cancer model were investigated. The expression of PKM2 in A549 cells was determined by immunofluorescence. PKM2 expression levels were evaluated by Western blot analysis. In a human A549 lung cancer xenograft model, the effects of treatment with shRNA, with or without cisplatin, on tumor volume were determined. Apoptosis and cell proliferation status were examined to determine the mechanisms of tumor growth inhibition. Expression of shRNA targeting PKM2 resulted in inhibition of PKM2 expression in A549 cells. In the lung cancer xenograft model, average tumor volume in the group treated with both cisplatin and shRNA was statistically lower than those of other groups (P < 0.05). The levels of apoptotic cells were significantly higher in samples from animals in the combined treatment group than those from untreated animals (P < 0.05). The cell proliferation rate, as determined by counting cells labeled with an anti-phospho-histone H3, a marker for mitosis, was lower in samples from animals treated with both cisplatin and shRNA than in samples from other groups (P < 0.05). Use of RNA interfering (RNAi) targeting PKM2 significantly inhibited tumor growth when combined with cisplatin in a human A549 lung cancer xenograft model. The enhanced antitumor activity of the combined treatment compared to treatment with shRNA alone may result in part from increased induction of apoptosis and augmented inhibition of cancer cell proliferation.

• Dosimetric comparison using different multileaf collimeters in intensity-modulated radiotherapy for upper thoracic esophageal cancer.

  Authors: Youling Gong, Shichao Wang, Lin Zhou, Yongmei Liu, Yong Xu, You Lu, Sen Bai, Yuchuan Fu, Qingfeng Xu, Qingfeng Jiang

  Radiation oncology (London, England). 01/2010; 5:65.

  To study the impacts of multileaf collimators (MLC) width [standard MLC width of 10 mm (sMLC) and micro-MLC width of 4 mm (mMLC)] in the intensity-modulated radiotherapy (IMRT) planning for the upperTo study the impacts of multileaf collimators (MLC) width [standard MLC width of 10 mm (sMLC) and micro-MLC width of 4 mm (mMLC)] in the intensity-modulated radiotherapy (IMRT) planning for the upper thoracic esophageal cancer (UTEC). 10 patients with UTEC were retrospectively planned with the sMLC and the mMLC. The monitor unites (MUs) and dose volume histogram-based parameters [conformity index (CI) and homogeneous index (HI)] were compared between the IMRT plans with sMLC and with mMLC. The IMRT plans with the mMLC were more efficient (average MUs: 703.1 +/- 68.3) than plans with the sMLC (average MUs: 833.4 +/- 73.8) (p < 0.05). Also, compared to plans with the sMLC, the plans with the mMLC showed advantages in dose coverage of the planning gross tumor volume (Pgtv) (CI 0.706 +/- 0.056/HI 1.093 +/- 0.021) and the planning target volume (PTV) (CI 0.707 +/- 0.029/HI 1.315 +/- 0.013) (p < 0.05). In addition, the significant dose sparing in the D5 (3260.3 +/- 374.0 vs 3404.5 +/- 374.4)/gEUD (1815.1 +/- 281.7 vs 1849.2 +/- 297.6) of the spinal cord, the V10 (33.2 +/- 6.5 vs 34.0 +/- 6.7), V20 (16.0 +/- 4.6 vs 16.6 +/- 4.7), MLD (866.2 +/- 174.1 vs 887.9 +/- 172.1) and gEUD (938.6 +/- 175.2 vs 956.8 +/- 171.0) of the lungs were observed in the plans with the mMLC, respectively (p < 0.05). Comparing to the sMLC, the mMLC not only demonstrated higher efficiencies and more optimal target coverage, but also considerably improved the dose sparing of OARs in the IMRT planning for UTEC.

• A Multicenter Retrospective Analysis of Survival Outcome Following Postoperative Chemoradiotherapy in Non-small-cell Lung Cancer Patients with N2 Nodal Disease.

  Authors: Bingwen Zou, Yong Xu, Tao Li, Wenhui Li, Bangxian Tang, Lin Zhou, Lu Li, Yongmei Liu, Jiang Zhu, Meijuan Huang, Jin Wang, Li Ren, Youlin Gong, Guowei Che, Lunxu Liu, Mei Hou, You Lu

  International journal of radiation oncology, biology, physics. 09/2009;

  PURPOSE: To retrospectively evaluate the role of postoperative chemoradiotherapy (POCRT) in patients with completely resected non-small-cell lung cancer (NSCLC) with N2 lymph node involvement.PURPOSE: To retrospectively evaluate the role of postoperative chemoradiotherapy (POCRT) in patients with completely resected non-small-cell lung cancer (NSCLC) with N2 lymph node involvement. METHODS AND MATERIALS: This study included 183 patients from four centers in southwest China who underwent radical section of Stage III-N2 NSCLC without any preoperative therapy. One hundred and four were treated with POCRT and 79 with postoperative chemotherapy (POCT) alone. The median radiation dose to clinical target volume (CTV) was 50 Gy (varying between 48 and 54 Gy), whereas the cycles of platinum-based chemotherapy ranged from two to six with a median of four. RESULTS: The median duration of follow-up was 72 months. The 5-year overall survival rate (OS) was 30.5% in the POCRT group, and 14.4% in the POCT group (p = 0.007). The 5-year disease-free survival rate (DFS) was 22.2% in POCRT group and 9.3% in POCT group (p = 0.003). In a multivariate analysis, N1 nodal involvement (N1+/N2+) was associated with significantly worse OS (HR = 1.454, 95% CI, 1.012-2.087, p = 0.043) and DFS (HR = 1.685, 95% CI, 1.196-2.372, p = 0.003). Absence of radiotherapy and treatment with fewer than three cycles of chemotherapy both were poor prognostic factors for both OS and DFS. CONCLUSIONS: As compared with chemotherapy alone, adjuvant treatment with both radiotherapy and chemotherapy improves survival in patients with completely resected Stage III-N2 nodal disease in NSCLC. Future study of treatment modality with radiotherapy and chemotherapy is warranted, especially focusing on both N1 and N2 nodal status.

• Characterization of a novel rat gene RTAP2a, screened by cross-reactive SEREX, restrictedly expressed in testis.

  Authors: Hanshuo Yang, Chunting Wang, Rui Wang, Hongxin Deng, Zhenyu Ding, Jinliang Yang, You Lu, Jiong Li, Peng Zhang, Yongqiu Mao, Bing Kan, Lin Wei, Feng Peng, Yuquan Wei

  Journal of bioscience and bioengineering. 07/2009; 107(6):589-95.

  Genes involved in tumorigenesis may be targets for cancer immunotherapy. For many tumor types, molecular signatures do not yet exist. Methods that identify novel, tissue-specific tumor-related genesGenes involved in tumorigenesis may be targets for cancer immunotherapy. For many tumor types, molecular signatures do not yet exist. Methods that identify novel, tissue-specific tumor-related genes therefore have potentially important implications for developing cancer immunotherapy. Here, we used cross-reactive serological analysis of recombinant cDNA expression (CR-SEREX) to identify the novel testicular cancer-related gene, rat testicular antigenic protein 2 (RTAP2). We identified two RTAP2 splice variants (RTAP2a and RTAP2b) encoding 191 and 358 amino acid proteins, respectively. RTAP2a and RTAP2b proteins have identical N-termini but different C-terminal regions arising from alternative splicing of exon 4. Bioinformatics and reverse transcription-polymerase chain reaction (RT-PCR) revealed that the RTAP2a transcript was expressed selectively in adult testis and several tumor cell lines, while RTAP2b was ubiquitous. Our results suggest that RTAP2a may contribute to testicular development and tumorigenesis, and may be a candidate gene for cancer immunotherapy.

• Endostar, a recombined humanized endostatin, enhances the radioresponse for human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts in mice.

  Authors: Qing-Lian Wen, Mao-Bin Meng, Bo Yang, Ling-Li Tu, Li Jia, Lin Zhou, Yong Xu, You Lu

  Cancer science. 06/2009;

  The purpose of this paper is to determine the efficacy of combining radiation therapy with endostar, a recombined humanized endostatin, in human nasopharyngeal carcinoma and human lung adenocarcinomaThe purpose of this paper is to determine the efficacy of combining radiation therapy with endostar, a recombined humanized endostatin, in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts. Tumor xenografts were established in the hind limb of male athymic nude mice (BALB/c-nu) by subcutaneous transplantation. The tumor-bearing mice were assigned into four treatment groups: sham therapy (control), endostar (20 mg/kg, once daily for 10 days), radiation therapy (6 Gray per day to 30 Gray, once a day for 1 week), and endostar plus radiation therapy (combination). The experiment was repeated and mice were killed at days 3, 6, and 10 after initiation therapy, and the tumor tissues and blood samples were collected to analyze the kinetics of antitumor, antiangiogenesis, and antivascularization responses of different therapies. In human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts, endostar significantly enhanced the effects of tumor growth inhibition, endothelial cell and tumor cell apoptosis induction, and improved tumor cell hypoxia of radiation therapy. Histological analyses demonstrated that endostar plus radiation also induced a significant reduction in microvascular density, microvascular area, and vascular endothelial growth factor and matrix metalloproteinase-2 expression compared with radiation and endostar alone respectively. We concluded that endostar significantly sensitized the function of radiation in antitumor and antiangiogenesis in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts by increasing the apoptosis of the endothelial cell and tumor cell, improving the hypoxia of the tumor cell, and changing the proangiogenic factors. These data provided a rational basis for clinical practice of this multimodality therapy. (Cancer Sci 2009).

• Primary pleomorphic rhabdomyosarcoma of trunk in an adolescent.

  Authors: Yongshun Chen, You Lu

  Journal of paediatrics and child health. 04/2009; 45(3):166-7.

• Beclin-1 Expression is a Predictor of Clinical Outcome in Patients with Esophageal Squamous Cell Carcinoma and Correlated to Hypoxia-Inducible Factor (HIF)-1alpha Expression.

  Authors: Yongshun Chen, You Lu, Changli Lu, Lei Zhang

  Pathology oncology research : POR. 02/2009;

  In the present study, we examined the relationship between Beclin-1 expression and HIF-1alpha expression in esophageal squamous cell carcinoma(ESCC). There was a loss of Beclin-1 protein expressionIn the present study, we examined the relationship between Beclin-1 expression and HIF-1alpha expression in esophageal squamous cell carcinoma(ESCC). There was a loss of Beclin-1 protein expression in 33% of ESCCs. Beclin-1 expression significantly correlated with depth of invasion, lymph node metastasis and clinical stage. Among the 54 patients, The survival rate of the Beclin-1-positive group was better than that of the Beclin-1-negative group. Twenty-five of the 54 (46%) tumor specimens showed high levels of HIF-1alpha immunoreactivity. Beclin-1 expression was associated with HIF-1alpha expression. The survival rate of patients with Beclin-1-positive and HIF-1alpha-low tumors was significantly higher than that of the other groups. These results suggest that Beclin-1 and HIF-1alpha expression are important determinants of survival in ESCCs.

• Phase II evaluation of nedaplatin and paclitaxel in patients with metastatic esophageal carcinoma.

  Authors: Youling Gong, Li Ren, Lin Zhou, Jiang Zhu, Meijuan Huang, Xiaojuan Zhou, Jin Wang, You Lu, Mei Hou, Yuquan Wei

  Cancer chemotherapy and pharmacology. 01/2009;

  PURPOSE: To evaluate the efficiency and toxicities of nedaplatin and paclitaxel in patients with metastatic carcinoma of the esophagus. METHODS: Thirty-nine untreated patients with confirmedPURPOSE: To evaluate the efficiency and toxicities of nedaplatin and paclitaxel in patients with metastatic carcinoma of the esophagus. METHODS: Thirty-nine untreated patients with confirmed metastatic tumors were enrolled. Patients were treated with nedaplatin 80 mg/m(2) and paclitaxel 175 mg/m(2) on day 1. Treatment was repeated every 21 days. RESULTS: Thirty-six patients were eligible to be evaluated to have had a response. The overall response rate was 43.6% (17/39), with complete response and partial response rates of 2.6 and 41%, respectively. The median progression-free survival and overall survival time was 6.1 and 10.3 months, respectively. Grade 3/4 toxicities were only observed in six patients [neutropenia in three patients (7.7%) and nausea/vomiting in three patients (7.7%)]. CONCLUSION: Comparing to other regimens, combination of nedaplatin and paclitaxel achieved an encouraging clinical outcome, with relatively minimal toxicities for patients with metastatic esophageal carcinoma.

• Liposomal honokiol inhibits VEGF-D-induced lymphangiogenesis and metastasis in xenograft tumor model.

  Authors: Jing Wen, A-Fu Fu, Li-Juan Chen, Xing-Jiang Xie, Guang-li Yang, Xian-Cheng Chen, Yong-Sheng Wang, Jiong Li, Ping Chen, Ming-Hai Tang, Xi Ming Shao, You Lu, Xia Zhao, Yu-Quan Wei

  International journal of cancer. Journal international du cancer. 01/2009;

  Lymph nodes metastasis of tumor could be a crucial early step in the metastatic process. Induction of tumor lymphangiogenesis by vascular endothelial growth factor-D may play an important role inLymph nodes metastasis of tumor could be a crucial early step in the metastatic process. Induction of tumor lymphangiogenesis by vascular endothelial growth factor-D may play an important role in promoting tumor metastasis to regional lymph nodes and these processes can be inhibited by inactivation of the VEGFR-3 signaling pathway. Honokiol has been reported to possess potent antiangiogenesis and antitumor properties in several cell lines and xenograft tumor models. However, its role in tumor-associated lymphangiogenesis and lymphatic metastasis remains unclear. Here, we established lymph node metastasis models by injecting overexpressing VEGF-D Lewis lung carcinoma cells into C57BL/6 mice to explore the effect of honokiol on tumor-associated lymphangiogenesis and related lymph node metastasis. The underlying mechanisms were systematically investigated in vitro and in vivo. In in vivo study, liposomal honokiol significantly inhibited the tumor-associated lymphangiogenesis and metastasis in Lewis lung carcinoma model. A remarkable delay of tumor growth and prolonged life span were also observed. In in vitro study, honokiol inhibited VEGF-D-induced survival, proliferation and tube-formation of both human umbilical vein endothelial cells (HUVECs) and lymphatic vascular endothelial cells (HLECs). Western blotting analysis showed that liposomal honokiol-inhibited Akt and MAPK phosphorylation in 2 endothelial cells, and downregulated expressions of VEGFR-2 of human vascular endothelial cells and VEGFR-3 of lymphatic endothelial cells. Thus, we identified for the first time that honokiol provided therapeutic benefit not only by direct effects on tumor cells and antiangiogenesis but also by inhibiting lymphangiogenesis and metastasis via the VEGFR-3 pathway. The present findings may be of importance to investigate the molecular mechanisms underlying the spread of cancer via the lymphatics and explore the therapeutical strategy of honokiol on antilymphangiogenesis and antimetastasis. (c) 2008 Wiley-Liss, Inc.

• [Construction of a recombinant adenovirus vector harboring human transforming growth factor-beta type II receptor-IgG1Fc fusion gene.]

  Authors: Li Jia, Jian-Xin Xue, You Lu

  Nan fang yi ke da xue xue bao = Journal of Southern Medical University. 01/2009; 28(12):2136-8.

  OBJECTIVE: To construct a recombinant adenoviral vector harboring human transforming growth factor-beta type II receptor-IgG1Fc (TbetaRII-IgG1Fc) fusion gene. METHODS: The cDNA fragments of humanOBJECTIVE: To construct a recombinant adenoviral vector harboring human transforming growth factor-beta type II receptor-IgG1Fc (TbetaRII-IgG1Fc) fusion gene. METHODS: The cDNA fragments of human TbetaRII and IgG1Fc genes were amplified by RT-PCR and fused with overlap PCR to obtain the fusion gene TbetaRKK-IgG1Fc. The TbetaRII-IgG1Fc gene was cloned into the shuttle plasmid pAdTrack-CMV, which was linearized and transfected into E.coli BJ 5183 strain containing the adenoviral backbone vector. The recombinant adenovirus vector was constructed by homologous recombination. The recombinant adenoviral plasmid was linearized and transfected into 293 cells, followed by amplification and purification of the virus and detection of TbetaRII-IgG1Fc mRNA expression by RT-PCR. The functional activity of the recombinant adenoviral plasmid was assessed using enzyme-linked immunosorbent assay (ELISA). RESULTS: The results of restriction endonuclease digestion and DNA sequencing indicated correct sequence of the target TbetaRII-IgG1Fc fusion gene. The recombinant adenoviral plasmid expressed hTbetaRII-IgG1Fc and neutralized TGF-beta1 in vitro after infection of the human lung fibroblasts (HLF), as confirmed by RT-PCR and ELISA. CONCLUSIONS: The recombinant adenoviral plasmid capable of neutralizing TGF-beta1 in vitro is constructed successfully.