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// Cuiling Zhou 1, * , Donglan Liu 2, * , Jie Li 3, * , Huanhuan Sun 1 , Xiaobin Zheng 4 , Shuncong Wang 1 , Guobin Hong 5 , Saradhi Mallampati 6 , Hongliu Sun 7 , Xiuling Zhou 1 , Zhibin Cheng 1 , Hongyu Zhang 1 , Haiqing Ma 1 1 Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China 2 Department of Gastroenterology, Cancer Hospital of Jiangxi Province, Nanchang, Jiangxi 330029, China 3 Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China 4 Department of Respiratory, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China 5 Department of Radiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China 6 Department of Laboratory Medicine and the Center for Stem Cell and Developmental Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA 7 Department of Pathology, University of Michigan, Ann Arbor, MI 48201, USA * These authors have contributed equally to this work Correspondence to: Haiqing Ma, email: mahaiqing@mail.sysu.edu.cn Hongyu Zhang, email: zdwyzhy@163.com Keywords: advanced non-small-cell lung cancer, overall survival, combination treatment of DC-CIKs, chemotherapy, meta-analysis Received: July 10, 2016 Accepted: November 07, 2016 Published: November 16, 2016 ABSTRACT This study was aimed to investigate the efficacy and safety of the combination treatment of dendritic cells co-cultured with cytokine-induced killer cells and chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC). Literatures were searched from the Cochrane Library Central, PubMed, Web of Science and EMBASE. The primary endpoint of interest was overall survival (OS), and secondary endpoints were disease control rate (DCR) and progression free survival (PFS). Finally 7 trials published between January 2005 and March 2016 met inclusion criteria and totally 610 patients were enrolled. The combination group showed advance in DCR (RR = 1.31, 95% CI = 1.13-1.52, p = 0.0004), 1-year OS (RR = 1.18, 95% CI = 1.05-1.33, p = 0.007), and 2-year OS (RR = 1.37, 95% CI = 1.10-1.70, p = 0.005), with statistical significance. The proportions of CD3 + T cells ( p = 0.002), NK cells ( p = 0.02) and NKT cells ( p = 0.001) were significantly higher in the peripheral blood of combination group, compared with those of the control group. Moreover, adverse reactions were obviously decreased in the combination group. However, no significant difference was identified in ORR and PFS between two groups ( p > 0.05). In conclusion, the combination therapy was safe and applicable for patients with advanced NSCLC.

// Xiaobin Zheng 1 , Neal Andruska 1,6 , Michael J. Lambrecht 2 , Sisi He 3 , Amadeo Parissenti 4 , Paul J. Hergenrother 2 , Erik R. Nelson 3,5 and David J. Shapiro 1,5,6 1 Department of Biochemistry University of Illinois, Urbana, IL, USA 2 Department of Chemistry, University of Illinois, Urbana, IL, USA 3 Department of Molecular Integrative Physiology, University of Illinois, Urbana, IL, USA 4 Cancer Research Program, Advanced Medical Research Institute of Canada, Sudbury, ON, Canada 5 University of Illinois Cancer Center, Urbana, IL, USA 6 College of Medicine, University of Illinois, Urbana, IL, USA Correspondence to: David J. Shapiro, email: // Keywords : ERα biomodulator, ATP depletion, unfolded protein response (UPR), MDR1/P-glycoprotein/ABCB1, OVCAR-3 ovarian cancer Received : May 02, 2016 Accepted : July 10, 2016 Published : July 24, 2016 Abstract Ovarian cancers often recur and tumors acquire resistance to chemotherapy due to overexpression of the ATP-dependent efflux pump, multidrug resistance protein 1 (MDR1/P-glycoprotein/ABCB1). Nontoxic small molecule inhibitors targeting MDR1 have remained largely elusive. Instead, in a novel application of our recently described estrogen receptor α (ERα) biomodulator, BHPI, we targeted MDR1’s substrate, ATP. BHPI depletes intracellular ATP and nearly blocks MDR1-mediated drug efflux in ovarian cancer cells by inducing toxic hyperactivation of the endoplasmic reticulum stress sensor, the unfolded protein response (UPR). BHPI increased sensitivity of MDR1 overexpressing multidrug resistant OVCAR-3 ovarian cancer cells to killing by paclitaxel by >1,000 fold. BHPI also restored doxorubicin sensitivity in OVCAR-3 cells and in MDR1 overexpressing breast cancer cells. In an orthotopic OVCAR-3 xenograft model, paclitaxel was ineffective and the paclitaxel-treated group was uniquely prone to form large secondary tumors in adjacent tissue. BHPI alone strongly reduced tumor growth. Notably, tumors were undetectable in mice treated with BHPI plus paclitaxel. Compared to control ovarian tumors, after the combination therapy, levels of the plasma ovarian cancer biomarker CA125 were at least several hundred folds lower; moreover, CA125 levels progressively declined to undetectable. Targeting MDR1 through UPR-dependent ATP depletion represents a promising therapeutic strategy.

// Beilong Zhong 1, * , Yan Lin 2, * , Yingrong Lai 3, * , Fangfang Zheng 4 , Xiaobin Zheng 5 , Rijiao Huang 6 , Weilin Yang 7 , Zhenguang Chen 7, 8, 9, * 1 Department of Thoracic Surgery, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong 519000, China 2 Department of Breast Disease, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China 3 Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China 4 Department of Pediatrics, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong 519000, China 5 Department of Respiratory Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong 519000, China 6 Department of Clinical Laboratory, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong 519000, China 7 Department of Cardiothoracic Surgery of East Division, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China 8 Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China 9 Lung Cancer Research Center of Sun Yat-sen University, Guangzhou, Guangdong 510080, China * These authors have contributed equally to this work Correspondence to: Zhenguang Chen, e-mail: chenzhenguang@yahoo.com Keywords: Oct-4, cancer staging, TNM staging, cancer grade of differentiation, meta-analysis Received: May 28, 2015 Accepted: October 28, 2015 Published: November 09, 2015 ABSTRACT Background: Octamer 4 (Oct-4), an important member of the POU domain transcription factor family, has been suggested to function as a master switch during differentiation of human somatic cells and more recently has come to be linked with neoplastic properties. The aim of this study was to evaluate the relationship between Oct-4 and cancer stage using a meta-analysis approach. Materials and Methods: Relevant articles published as of May 2015 were retrieved from the following databases: PubMed, ISI Web of Knowledge, Embase, and Chinese National Knowledge Infrastructure (CNKI). The strengths of relationship for outcomes of interest were estimated based on odds ratios (ORs) and 95% confidence intervals (CIs). Results: A total of 11 articles on Oct-4 and cancer staging that collectively included 502 positive/high Oct-4 cases and 522 negative/low case-free controls were chosen. Positive/high Oct-4 was significantly associated with cancer stage in several kinds of cancer. Specifically, positive/high Oct-4 was associated with cancer stage III/IV (fixed effects: OR = 1.53, 95% CI = 1.12–2.10), primary tumor (T 3–4 ) (random effects: OR = 1.93, 95% CI = 0.99–3.77), and cancer grade of differentiation (intermediate-poor) (random effects: OR = 3.45, 95% CI = 1.5–7.61). Conclusion: These findings suggest that positive/high Oct-4 is more strongly linked to stage III/IV cancer and cancer grade of differentiation, and is correlated with malignant characteristics that lead to poor prognosis in different types of cancer, especially in Asian. Given variability related to ethnicity and differences in cancer types, additional studies are warranted to establish the generalizability of our findings.

// Beilong Zhong 1,* , Tao Wang 2,3,* , Jianyong Zou 4,5,* , Fangfang Zheng 6 , Rijiao Huang 7 , Xiaobin Zheng 8 , Weilin Yang 9 and Zhenguang Chen 4,5,9,* 1 Department of Thoracic Surgery, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China 2 Center for Stem Cell Biology and Tissue Engineering, Sun Yat-sen University, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Guangzhou, Guangdong, China 3 Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou, Guangdong, China 4 Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China 5 Lung Cancer Research Center of Sun Yat-sen University, Guangzhou, Guangdong, China 6 Department of Pediatrics, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China 7 Department of Clinical Laboratory, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China 8 Department of Respiratory Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China 9 Department of Cardiothoracic Surgery of East Division, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China * These authors have contributed equally to this work Correspondence to: Zhenguang Chen, email: // Keywords : nestin, intermediate filament, cancer stage, TNM staging, meta-analysis Received : February 28, 2015 Accepted : April 20, 2015 Published : May 08, 2015 Abstract Background: Nestin, a member of the intermediate filament protein family, has been reported to be associated with several types of neoplastic transformation. However, questions remain, with studies reporting sometimes inconclusive or conflicting data. Thus, the aim of this study was to evaluate literature reports on the relationship between nestin and cancer stage. Methods: Relevant articles published as of June 2014 were retrieved from multiple databases. After applying specific inclusion criteria, we chose seven articles relating to nestin expression and cancer stage, which included a total of 223 positive/high nestin cases and 460 negative/low case-free controls. Results: Overall, positive/high nestin was significantly associated with median or advanced stages of several types of cancer (nestin and cancer stage: OR = 1.90, 95% CI = 1.30–2.78; nestin and lymph node: OR = 2.17, 95% CI = 1.26–3.72). Notably, studies relating to lung cancer (three qualifying articles) showed a significant association between nestin and lung cancer stage (OR = 2.00, 95% CI = 1.16–3.44). Conclusion: These findings indicate that positive/high nestin may be more strongly linked to median or advanced cancer stage and correlated with malignant characteristics that lead to poor prognosis in different cancers, especially lung cancer.

// Cuiling Zhou 1, * , Jianjun Tang 2, * , Huanhuan Sun 1, * , Xiaobin Zheng 3 , Zhanyu Li 4 , Tiantian Sun 5 , Jie Li 6 , Shuncong Wang 1 , Xiuling Zhou 1 , Hongliu Sun 7 , Zhibin Cheng 1 , Hongyu Zhang 1 and Haiqing Ma 1 1 Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China 2 Department of Gastroenterology, Cancer Hospital of Jiangxi Province, Nanchang, Jiangxi 330029, China 3 Department of Respiration, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China 4 Department of Pathology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China 5 Department of Hematology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China 6 Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China 7 Department of Pathology, University of Michigan, Ann Arbor, MI 48201, USA * These authors have contributed equally to this work Correspondence to: Haiqing Ma, email: mahaiqing@mail.sysu.edu.cn Hongyu Zhang, email: zdwyzhy@163.com Keywords: NSCLC, PD-L1, survival, prognostic factor, histologic type Received: August 29, 2016 Accepted: March 22, 2017 Published: April 11, 2017 ABSTRACT Objectives: The role of programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC), especially according to histologic type, remains controversial. The purpose of this study was to assess PD-L1 expression and its association with overall survival (OS) and clinicopathologic characteristics in NSCLC. Materials and methods: Formalin-fixed paraffin-embedded specimens were obtained from 108 patients with surgically resected primary NSCLC. PD-L1 expression was assessed via immunohistochemistry using a histochemistry score system. The relationship between OS or clinicopathologic characteristics and PD-L1 expression was evaluated via the Kaplan-Meier method and Cox proportional hazards model, respectively. Results: Of 108 NSCLC specimens, 44 had high PD-L1 expression, which was highly associated with histologic type ( p = 0.003). Patients without PD-L1 expression had remarkably longer OS than those with PD-L1 expression (median OS: 96 months vs. 33 months, p < 0.001). In the subgroup analysis of non-squamous cell carcinoma, OS was more favorable in those without PD-L1 expression than in those with PD-L1 expression (median OS: 113 months vs. 37 months, p < 0.001). Multivariate analysis revealed that PD-L1 expression (95% confidence interval 1.459-4.520, p < 0.001), male sex and higher tumor-node-metastasis stage were significantly correlated with shorter OS. Conclusions: This study demonstrated that PD-L1 expression is an independent prognostic factor for poor survival in NSCLC patients, especially those with non-squamous NSCLC.