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Zhuojun Yu, 1–3,* Huichuan Yu, 1,* Qi Zou, 1, 4 Zenghong Huang, 1, 2 Xiaolin Wang, 1 Guannan Tang, 1 Liangliang Bai, 1 Chuanhai Zhou, 1–3 Zhuokai Zhuang, 1, 2 Yumo Xie, 1, 2 Heng Wang, 1 Gaopo Xu, 1 Zijian Chen, 1, 5 Xinhui Fu, 1, 6 Meijin Huang, 1, 2 Yanxin Luo 2 1Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, People’s Republic of China; 2Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, People’s Republic of China; 3Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510655, People’s Republic of China; 4Department of Colorectal and Anal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, People’s Republic of China; 5Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, People’s Republic of China; 6Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huichuan YuGuangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, Guangdong 510655, People’s Republic of ChinaTel +86-18302044819Email yuhch5@mail.sysu.edu.cnYanxin LuoDepartment of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, Guangdong 510655, People’s Republic of ChinaTel +86-13826190263Email luoyx25@mail.sysu.edu.cnBackground: Colorectal cancer (CRC) patients with different molecular phenotypes, including microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and somatic mutations in BRAF and KRAS gene, vary in treatment response and prognosis. However, molecular phenotyping under adequate quality control in a community-based setting may be difficult. We aimed to build the nomograms based on easily accessible clinicopathological characteristics to predict molecular phenotypes.Methods: Three hundred and six patients with pathologically confirmed stage I-IV CRC were included in the cohort. The assays for MSI, CIMP, and mutations in BRAF and KRAS gene were performed using resected tumor samples. The candidate predictors were identified from clinicopathological variables using multivariate Logistic regression analyses to construct the nomograms that could predict each molecular phenotype.Results: The incidences of MSI, CIMP, BRAF mutation and KRAS mutation were 25.3% (72/285), 2.5% (7/270), 3.4% (10/293), and 34.8% (96/276) respectively. In the multivariate Logistic analysis, poor differentiation and high neutrophil/lymphocyte ratio (NLR) were independently associated with MSI; poor differentiation, high NLR and high carcinoembryonic antigen/tumor size ratio (CSR) were independently associated with CIMP; poor differentiation, lymphovascular invasion and high CSR were independently associated with BRAF mutation; poor differentiation, proximal tumor, mucinous tumor and high NLR were independently associated with KRAS mutation. Four nomograms for MSI, CIMP, BRAF mutation and KRAS mutation were developed based on these independent predictors, the C-indexes of which were 61.22% (95% CI: 60.28– 62.16%), 95.57% (95% CI: 95.20– 95.94%), 83.56% (95% CI: 81.54– 85.58%), and 69.12% (95% CI: 68.30– 69.94%) respectively.Conclusion: We established four nomograms using easily accessible variables that could well predict the presence of MSI, CIMP, BRAF mutation and KRAS mutation in CRC patients.Keywords: colorectal cancer, microsatellite instability, CpG island methylator phenotype, BRAF, KRAS, nomogram, prediction of molecular subtypes &nbsp

Huanrong Hu1,2 Zhen Dong,2–4 Xianxing Wang,2–4 Longchang Bai,2–4 Qian Lei,2–4 Jie Yang,2–4 Lin Li,2–4 Qian Li1,2, Lichao Liu1,2 Yanli Zhang,1 Yacong Ji,1 Leiyang Guo,1 Yaling Liu,1 Hongjuan Cui2–41Department of Dermatology, the Third Hospital of Hebei Medical University, Shijiazhuang 050000, People’s Republic of China; 2State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, People’s Republic of China; 3Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing 400715, People’s Republic of China; 4Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative Medicine, Southwest University, Chongqing 400715, People’s Republic of ChinaPurpose: Alkaloids are naturally occurring chemical compounds that are widely distributed in plants, and have pharmaceutical values and low toxicity. In recent years, some of them have been demonstrated to be promising therapeutic drug candidates for cancer treatment. Herein, we tried to explore the antitumor effect of dehydrocorydaline (DHC), a natural alkaloid isolated from Corydalis, on malignant melanoma.Methods: We treated two malignant metastatic melanoma cell lines, A375 and MV3, and a normal melanocyte cell line, PIG1, with various concentrations of DHC for set amounts of time, and detected cell proliferation, migration, and invasion by using MTT, BrdU, transwell, Western blot and soft agar assay in vitro and tumorigenicity in the xenografts in vivo.Results: Our results showed that DHC dramatically blocked cell proliferation and led to cell cycle arrest at G0/G1 phase and downregulated the expressions of cell cycle regulators CDK6 and Cyclin D1 in melanoma cells. However, DHC had little inhibitory effect on normal melanocyte cell line PIG-1. Meanwhile, DHC suppressed cell invasion and migration through modulating the epithelial–mesenchymal transition (EMT) markers including E-cadherin, vimentin, as well as β-catenin. In addition, DHC also significantly attenuated tumor growth in vivo. The expressions of cell cycle-related and metastasis-related proteins were further confirmed by immunohistochemical staining in the xenografts. Importantly, MEK1/2-ERK1/2 cascade was inactivated after DHC treatment and ERK activator t-butylhydroquinone (tBHQ) treatment rescued DHC-induced cell proliferation inhibition.Conclusions: Our results indicated that DHC inhibited cell proliferation and migration/invasion via inactivating MAPK signaling, and showed that DHC might be a potential novel drug to treat malignant melanoma.Keywords: dehydrocorydaline, melanoma, cell cycle, migration and invasion, MAPK

Hu H, Dong Z, Wang X, et al. Onco Targets Ther. 2019;12:5163–5175. The authors have advised due to an error at the time of figure assembly, Figures 2G and 4A on pages 5167 and 5169, respectively is incorrect. The correct Figures 2 and 4 are shown in Download Article. The authors apologize for these errors and advise it does not affect the results of the paper. Read the original article

Wen Q, Zhao L, Wang T, et al. Onco Targets Ther. 2019;12:699–708. At the request of the authors, the Editor and Publisher of OncoTargets and Therapy wish to retract the published article. Since publication the authors have been unable to reproduce the results reported in this article. The authors were also unable to locate all the original raw data for their study and to ensure the integrity of the publication record requested to retract the article. The Editor has agreed with this decision. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Qiang Wen,1,* Lina Zhao,2,* Tongtong Wang,1 Ningning Lv,1 Xuejiao Cheng,1 Guang Zhang,2 Lin Bai1 1Department of Nuclear Medicine, China-Japan Union Hospital of Jilin University, ErDao District, Changchun 13033, China; 2Department of Thyroid Surgery, China-Japan Union Hospital of Jilin University, ErDao District, Changchun 13033, China *These authors contributed equally to this work Background: Long noncoding small nucleolar RNA host gene 16 (SNHG16) has been shown to play an oncogenic role in multiple cancers. However, the biological roles and mechanism of SNHG16 action in the regulation of papillary thyroid cancer (PTC) remains unknown. The aims of this study were to investigate the roles and the possible mechanism of SNHG16 in PTC progression. Materials and methods: The expression of SNHG16 PTC tissues and cell lines was detected by reverse-transcription quantitative PCR (qRT-PCR). The effect of SNHG16 on cell proliferation, apoptosis, migration, and invasion was detected by Cell Counting Kit-8, flow cytometry, wound-healing assay, and Matrigel invasion assay, respectively. In addition, the regulatory relationships between SNHG16 and miR-497 were explored by luciferase reporter assay and qRT-PCR. Results: The SNHG16 expression was upregulated in PTC tissues and cell lines, whose expression was positively associated with advanced TNM stage and lymph node metastasis. Function analysis demonstrated that depletion of SNHG16 in PTC cells significantly inhibited cell proliferation, induced cell apoptosis, and suppressed cell migration and invasion abilities. Mechanistic studies indicated that SNHG16 functioned as an endogenous sponge for miR-497 to regulate its target genes brain-derived neurotrophic factor and yes-associated protein 1 expression. Furthermore, the inhibition of miR-497 antagonized the suppressive effect of SNHG16-depleted cells on cell proliferation, migration, and invasion. Conclusion: These findings revealed that SNHG16 drived the PTC progression possibly via regulating miR-497, suggesting that SNHG16 might be a novel therapeutic agent for PTC. Keywords: papillary thyroid cancer, long noncoding RNAs, SNHG16, miR-497

Weiguo Xiang,1 Chao-Yie Yang,1,2 Longchuan Bai1,2 1Department of Internal Medicine, University of Michigan Medical School, 2Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA Abstract: Myeloid cell leukemia-1 (MCL-1), a member of antiapoptotic BCL-2 family proteins, is a key regulator of mitochondrial homeostasis. Frequent overexpression of MCL-1 in human primary and drug-resistant cancer cells makes it an attractive cancer therapeutic target. Significant progress has been made in the development of small-molecule MCL-1 inhibitors in recent years, and three MCL-1 selective inhibitors have advanced to clinical trials. This review briefly discusses recent advances in the development of small molecules targeting MCL-1 for cancer therapy. Keywords: BCL-2, BAX, BAK, apoptosis, BH3 mimetics

Zeyu Wang,1 Jing Zhang,2 Zhiguang Zhang,2 Yong Jiang,2 Man Li,2 Qian Li,2 Lu Bai,2 Dongying Yao,1 Miao Wang,1 Xiaoping Wang1 1Department of Gastroenterology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, 201318, China; 2Department of Gastroenterology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, China Background: There are accumulating studies investigating the aberrant expression of microRNAs in tumor patients. As an important member of miR-17/92 cluster, miR-17-5 p has been identified as a potential prognostic factor for survival in tumor patients. We conducted this meta-analysis aimed to assess the effect of miR-17-5 p as a prognostic biomarker for gastrointestinal tumor patients. Materials and methods: Eligible studies were enrolled by searching the online databases of PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and WanFang Data until September 2017. We calculated pooled hazard ratios (HRs) and 95% CI of miR-17-5 p for overall survival and disease-free survival. Results: In the categorical variable analysis, we identified 11 studies with 1,279 patients. The pooled analyses suggested that overexpression of miR-17-5 p may predict poor overall survival (HR = 1.86, 95% CI: 1.55–2.25, P

Dongqi Gao, Jingjing Zhang, Lu Bai, Fubo Li, Yi Dong, Qingshan Li Department of Oncology, Affiliated Hospital of Chengde Medical University, Chengde 067000, China Background: Non-small-cell lung cancer (NSCLC) has one of the highest mortality rates among cancers worldwide, with a poor prognosis. Previous studies have reported that melittin, an active component of apitoxin, exerts anti-inflammatory and antitumor effects via vascular endothelial growth factor or FoxO1. Methods: CCK8, flow cytometry assay and Western blotting were performed to evaluate the effect of melittin on NSCLC. Results: The present study demonstrates that melittin activated caspase-2 by inhibiting miR-183 expression and, thus, induced NSCLC apoptosis in both NCI-H441 cancer cell line assays and an in vivo xenograft model. The results of the cell-based assays showed that melittin (2 µg/mL) robustly suppressed miR-183 expression level and resulted in decreased invasion and migration abilities of NCI-H441 cells. Additionally, a flow cytometry assay and Western blotting showed that melittin induced NSCLC NCI-H441 cell apoptosis along with significant elevation of caspase-2 and Bax, which are regulators of cell apoptosis, and reduced Bcl-2 protein expression compared with dimethyl sulfoxide control. Furthermore, subcutaneous injection of melittin (5 mg/kg) significantly suppressed NSCLC tumor growth compared with vehicle group tumors, determined through tumor size and weight. Conclusion: Taken together, the aforementioned findings contribute to identification of a novel therapeutic target in the treatment of NSCLC, in patients diagnosed with a high expression of miR-183. Moreover, this article provides solid evidence for the inhibitory effect of melittin on NSCLC cancer cell growth. Keywords: miR-183, melittin, NSCLC, caspase 2, apoptosis

Sen Wang, Wei-Cheng Gao, San-San Chen, Liang Bai, Li Luo, Xiang-Guang Zheng, You Luo Department of Urology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China Objective: To define the survival effect of surgery of primary adrenal malignant lesions in metastatic adrenocortical carcinoma (ACC) patients. Patients and methods: We used the Surveillance, Epidemiology and End Results (SEER) database (1973–2014) to identify metastatic ACC patients (stage IV by using European Network for the Study of Adrenal Tumors stage classification). Correlated variables, including age, sex, race, tumor laterality, treatment modality, lymph node dissection, surgery of metastatic site, tumor size, and tumor stage, were extracted. Univariate and multivariate Cox regression analyses were used to define the efficacy of surgery on survival outcomes, including overall survival and cancer-specific survival of ACC. Results: There were 290 metastatic ACC patients identified from the database. The overall median survival time was 7 (95% CI, 6–8) months. Among these patients, 118 patients received primary site surgery and 172 patients did not. In both univariate and multivariate analyses, primary site surgery significantly improved both overall (hazard ratio 0.413, 95% CI, 0.299–0.571, P

Lu Bai,1,* Chihua Guo,2,* Jiansheng Wang,3 Xiang Liu,1 Yang Li,1 Miao Li,1 Youmin Guo,2 Xiaoyi Duan2 1Department of Medical Imaging, 2Department of Orthopedics, 3Department of Oncological Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China *These authors contributed equally to this work Objective: Metabolic activity and tumor burden are significant for prognosis and metastasis of non-small cell lung cancer (NSCLC), including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Chemotherapy resistance is a great challenge for treating NSCLC patients and is also closely related with several biomarkers such as epidermal growth factor receptor (EGFR), p53, and excision repair cross-complementing group 1 protein (ERCC1). Our purpose was to determine the correlation between positron emission tomography/computed tomography (PET/CT) parameters and tumor markers-related chemotherapy resistance in NSCLC. Methods: Forty-six NSCLC chemotherapy-naïve patients were enrolled. The SUVmax, MTV, and TLG were calculated by PET/CT imaging, and expression of EGFR, p53, and ERCC1 were analyzed by immunohistochemistry on tissues. SUVmax, MTV, and TLG compared for their performance in predicting the expression of EGFR, p53, and ERCC1 were illustrated with statistical analysis. Results: SUVmax was significantly correlated with p53 expression (P=0.001), and MTV and TLG were significantly associated with ERCC1 (P=0.000; P=0.000). Furthermore, multiple stepwise regression analysis revealed that SUVmax was the primary predictor for p53, MTV and TLG was the primary predictor for ERCC1. SUVmax had a sensitivity of 91% and specificity of 50% for the detection of p53 positive. The sensitivities of MTV and TLG were 83% and 80%, and specificities were 69% and 75% for the detection of ERCC1 positive, respectively. When we suggested p53 or ERCC1 positive, the cutoff value of SUVmax, MTV, and TLG were 7.68, 23.62, and 129.65 cm3, respectively. Conclusion: SUVmax, MTV, and TLG were closely associated with p53 and ERCC1’ expressions. Therefore, 18F-fludrodeoxyglucose PET/CT could be a new way of predicting p53 or ERCC1-related chemotherapy effect in NSCLC patients with more convenience. Keywords: non-small cell lung cancer, tumor markers, 18F-fludrodeoxyglucose, total lesion glycolysis, metabolic tumor volume, maximal standardized uptake values

Feng Wang,* Feng-Hua Wang,* Long Bai, Rui-Hua XuDepartment of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China *These authors contributed equally to this workAbstract: The China Food and Drug Administration approved the use of capecitabine in patients with metastatic colorectal cancer (mCRC) in 2004. This paper reviews the available information of capecitabine in Chinese patients with mCRC, focusing on its effectiveness and safety against mCRC. Identification of all eligible studies was made by searching the PubMed and Wanfang database from 2000 to 2013. Published data examining various aspects of clinical response and tolerability with capecitabine alone or in combination with other chemotherapeutic or biological agents for first- and second-line mCRC were examined. Capecitabine and its combination displayed high efficacy in Chinese patients with mCRC. Toxicities are generally manageable, and elderly patients can tolerate capecitabine well.Keywords: capecitabine, metastatic colorectal cancer, Chinese