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Sun F, Wu K, Yao Z, et al. Onco Targets Ther. 2020;13:6755–6765. We, the Editors and Publisher of OncoTargets and Therapy, have retracted the following article. Since publication, concerns have been raised about the integrity of the data in the article. This includes the duplication of images from Figures 5 and 6. Specifically, The image for Figure 5C, NC, has overlap with the image for Figure 6D, NC. When approached for an explanation, the authors did not respond to our queries, nor did they provide original data for their study. As verifying the validity of the published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors were notified of this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Weiyan Zou,1 Jie Zhao,2 Yi Li,2 Zishu Wang,3 Haiqin Yan,1 Yudong Liu,1 Meiqun Sun,1 Jialu Zhuang,2 Junbin Wang3 1Department of Histology and Embryology, Bengbu Medical College, Bengbu 233004, Anhui Province, People’s Republic of China; 2The Second School of Clinical Medicine, Bengbu Medical College, Bengbu 233004, Anhui Province, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, Anhui Province, People’s Republic of ChinaCorrespondence: Junbin Wang Email bbmcwjb@163.comBackground: Colorectal cancer is one of the most common cancers and the second leading cause of cancer-related deaths worldwide. Targeting cancer stem cells (CSCs) may be a novel strategy for the treatment of colorectal cancer. Previous studies have shown that bone marrow-derived MSCs (BM-MSCs) promote tumor growth and metastasis. However, the role of rat BM-MSCs in the biological behaviors of colorectal CSCs remains unclear until now.Materials and Methods: BM-MSCs were isolated from rats and characterized. CSCs were enriched from HCT116 cells using the microsphere culture method, and the microspheres incubated for at least 10 passages were termed HCT116-CSCs that were characterized. The effects of rat BM-MSCs on migration and invasion of HCT116-CSCs were examined using transwell migration and invasion assays and xenograft tumor growth assay.Results: Rat BM-MSCs appeared typical stem cell morphology. Flow cytometry revealed positive CD29 and CD44 expression in rat BM-MSCs at passage 3, and rat BM-MSCs were found to differentiate into osteocytes following incubation in osteogenic induction medium. Microscopy, flow cytometric detection of stem cell surface markers, colony-formation assay and transwell migration and invasion assays characterized the successful preparation of HCT116-CSCs, and subcutaneous injection of HCT116-CSCs produced xenograft tumors in nude mice, while HE staining of the xenograft tumors displayed cancer specimen shapes. Transwell migration and invasion assays showed that rat BM-MSCs promoted the migration and invasion of HCT116-CSCs, and injection of rat BM-MSCs was found to promote the growth of the mouse xenograft tumor derived from HCT116-CSCs.Conclusion: Rat BM-MSCs promote the migration and invasion of colorectal CSCs, and colorectal CSCs may be a potential target for the therapy against colorectal cancer.Keywords: bone marrow-derived mesenchymal stem cells, colorectal cancer, cancer stem cells, migration, invasion

Feng Sun, Ke Wu, Zhixian Yao, Xingyu Mu, Zhong Zheng, Menghao Sun, Yong Wang, Zhihong Liu, Yiyong Zhu Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People’s Republic of ChinaCorrespondence: Yiyong Zhu; Ke WuDepartment of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People’s Republic of ChinaTel +86 15902190823; +86 15800567782Email zyy1017@hotmail.com; doctorwuke@sjtu.edu.cnBackground: Metastatic disease caused by prostate cancer (PCa) is the principal cause of PCa-related mortality. Long non-protein-coding RNAs may possess significant cellular functions. Plasmacytoma variant translocation 1 (PVT1), a long non-coding RNA encoded by the human PVT1 gene, is an oncogene, which can regulate several tumor-related genes. In PCa, the function and mechanism of PVT1 are unclear. NOP2 is being pursued as a prognostic marker for cancer aggressiveness, which promotes mouse fibroblast growth and tumor formation. Essentially, nothing is known about the specific interactions between the PVT1 and NOP2.Methods: 190 pairs of PCa tissues and adjacent normal tissues were collected and RNA sequencing was used to identify the differential lncRNAs. Real-time quantitative real-time PCR (RT-qPCR) confirmed these results and gene regulatory relationship. Lentiviral vectors were used to alter PVT1 and genes to analyze their effects on PCa progression. Transwell migration and invasion assays were performed to test the metastasis ability. Biofunction of PVT1 and NOP2 were confirmed in vitro and in vivo.Results: In this study, we reported that the long noncoding RNA-PVT1 was upregulated in PCa metastasis tissues and promoted migration of PCa cells in vitro and their metastasis in vivo. High levels of PVT1 significantly downregulated tumor suppressor microRNAs (miRNAs), such as miR-15b-5p, miR-27a-3p, miR-143-3p, and miR-627-5p, whose levels in metastasis tissues were low compared to those in non-metastasis tissues. In vitro and in vivo, PVT1 promotes PCa metastasis via targeting miRNAs. Furthermore, the expression level of PVT1 was positively associated with the expression of NOP2, a cancer metastasis-related protein. We demonstrated that NOP2 promoted invasion and migration of PCa. For specific mechanism, correlation analysis showed that PVT1 promoted metastasis by up-regulating NOP2.Conclusion: Taken together, our results show that PVT1 acts as an inducer of PCa metastasis via targeting miRNAs, thereby promoting NOP2. This axis may have diagnostic and therapeutic potential for advanced PCa.Keywords: lncRNA PVT1, miRNAs, NOP2, metastasis, prostate cancer

Wei Liu,1,2 Lei Zhang,1,2 Zhiming Xiu,2 Jian Guo,1 Liye Wang,3 Yue Zhou,4 Yang Jiao,1 Meiyan Sun,1 Jianhui Cai1,2 1College of Laboratory Medicine, Jilin Medical University, Jilin 132013, People’s Republic of China; 2Jilin Collaborative Innovation Center for Antibody Engineering, Jilin Medical University, Jilin 132013, People’s Republic of China; 3Department of Pharmacological and Pharmaceutical Science, College of Pharmacy, University of Houston, Houston, TX 77030, USA; 4Department of Statistics, North Dakota State University, Fargo, ND 58102, USACorrespondence: Jianhui Cai; Meiyan Sun Email caijianhui19640917@163.com; sunmy990@163.comAbstract: Tremendous progress has been achieved in the field of immune checkpoint inhibitors (ICIs) therapy in lung cancer in recent years. To generate robust, long-lasting anti-tumor immune responses in lung cancer patients, combinational ICI therapies have been explored deeply. Conventionally, chemotherapy was considered as immunosuppressive. It is now recognized that chemotherapy could also reinstate cancer cell immune-surveillance and enable the perception of cancer cells as dangerous. That is to say that chemotherapeutic drugs are not only a source of direct cytotoxic effects but also an adjuvant for anti-tumor immunity. Recently, multiple clinical studies of ICIs combined with chemotherapeutic drugs have been explored and proved effective. However, there are still crucial questions that are not well addressed, such as the optimal dose and schedule for a given combination may differ across disease indications, and the appropriate strategy of selecting patient population that can benefit from ICIs remains unclear. To facilitate more rational lung cancer ICIs therapy development, this review summarizes the immune-regulatory effects and related mechanisms of chemotherapeutic drugs and the clinical progress of ICIs and their combination with chemotherapies in lung cancer treatment.Keywords: ICIs therapy, chemotherapy, lung cancer, immunomodulation

Lu Chen, Xin Jiang, Haoyue Chen, Qiaoyan Han, Chunhua Liu, Miao Sun Department of Hematology, Jingjiang People’s Hospital, The Seventh Affiliated Hospital of Yangzhou University, Jiangsu 214500, P.R. China Background: A variety of microRNAs (miRNAs) are aberrantly expressed in acute myeloid leukemia (AML), and these dysregulated miRNAs perform crucial roles in tumorigenesis and progression of AML. miR-628-3p (miR-628), one of the miRNAs dysregulated in multiple types of human cancers, exerts antitumor roles in different cancer types. However, no specific study has explored the expression pattern and role of miR-628 in AML. Materials and methods: In this study, RT-qPCR was performed to detect miR-628 expression in AML tissues and cell lines. CCK-8 assay, flow cytometry analysis and xenograft tumor experiment was carried out to determine the functions of miR-628 in AML cells. The possible mechanism underlying the activity of miR-628 in AML cells was also explored using a series of experiments. Results: Our results revealed the downregulated expression of miR-628 in patients with AML and AML cell lines. Ectopic expression of miR-628 resulted in the inhibition of AML cell proliferation and induction of cell cycle arrest and apoptosis in vitro and attenuation of tumor growth in vivo. Insulin-like growth factor 1 receptor (IGF-1R) was identified as a direct target gene of miR-628 in AML cells. IGF-1R expression was upregulated in patients with AML and upregulation of IGF-1R expression inversely correlated with miR-628 level. Furthermore, IGF-1R knockdown imitated the tumor suppressive effect of miR-628 in AML cells. Restoration of IGF-1R expression abrogated the effects of miR-628 on the proliferation, cycle status, and apoptosis rate of AML cells. miR-628 inhibited the activation of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt) pathway in AML cells both in vitro and in vivo through the inhibition of IGF-1R expression. Conclusion: Our results demonstrate that miR-628 exhibits antitumor effects in AML through the direct targeting of IGF-1R and regulation of PI3K/Akt pathway, suggestive of its potential role as a therapeutic target in patients with this aggressive hematological malignant tumor. Keywords: acute myeloid leukemia, microRNA-628, proliferation, cell cycle, apoptosis, insulin-like growth factor 1 receptor, PI3K/Akt pathway

Zhijing Na,1,* Xinbo Qiao,1,* Xuanyu Hao,2 Ling Fan,3 Yao Xiao,4 Yining Shao,4 Mingwei Sun,4 Ziyi Feng,4 Wen Guo,4 Jiapo Li,1 Jiatong Li,5 Dongyang Li6 1Department of Post-graduate, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People’s Republic of China; 2Department of Rheumatology and Immunology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110022, People’s Republic of China; 3Department of Nursing, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People’s Republic of China; 4The First Clinical Department of China Medical University, Shenyang, Liaoning 110122, People’s Republic of China; 5Department of Undergraduate, The First Clinical Academy of China Medical University, Shenyang, Liaoning 110001, People’s Republic of China; 6Department of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People’s Republic of China *These authors contributed equally to this work Background: Beta-blockers are antihypertensive drugs and have shown potential in cancer prognosis. However, this benefit has not been well defined due to inconsistent results from the published studies.Methods: To investigate the association between administration of beta-blocker and cancer prognosis, we performed a meta-analysis. A literature search of PubMed, Embase, Cochrane Library, and Web of Science was conducted to identify all relevant studies published up to September 1, 2017. Thirty-six studies involving 319,006 patients were included. Hazard ratios were pooled using a random-effects model. Subgroup analyses were conducted by stratifying ethnicity, duration of drug use, cancer stage, sample size, beta-blocker type, chronological order of drug use, and different types of cancers.Results: Overall, there was no evidence to suggest an association between beta-blocker use and overall survival (HR=0.94, 95% CI: 0.87–1.03), all-cause mortality (HR=0.99, 95% CI: 0.94–1.05), disease-free survival (HR=0.59, 95% CI: 0.30–1.17), progression-free survival (HR=0.90, 95% CI: 0.79–1.02), and recurrence-free survival (HR=0.99, 95% CI: 0.76–1.28), as well. In contrast, beta-blocker use was significantly associated with better cancer-specific survival (CSS) (HR=0.78, 95% CI: 0.65–0.95). Subgroup analysis generally supported main results. But there is still heterogeneity among cancer types that beta-blocker use is associated with improved survival among patients with ovarian cancer, pancreatic cancer, and melanoma.Conclusion: The present meta-analysis generally demonstrates no association between beta-blocker use and cancer prognosis except for CSS in all population groups examined. High-quality studies should be conducted to confirm this conclusion in future. Keywords: cancer, prognosis, beta-blocker, meta-analysis

Ming Sun,1 Wenyan Zhao,2 Yuecan Zeng,3 Di Zhang,4 Zhaofu Chen,1 Caigang Liu,5 Bin Wu1 1Department of Urology, 2Department of General Surgery, 3Department of Medical Oncology, Shengjing Hospital of China Medical University, 4Department of Pathology, the First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, 5Department of Breast Cancer Surgery Center, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China Abstract: The study aimed to investigate the clinical significance of fibrous sheath interacting protein 1 (FSIP1) in bladder cancer, and its potential relevance to the survival of patients with bladder cancer. A total of 225 surgical excised-bladder cancer tissues were collected from the patients with the follow-up data >5 years. The FSIP1 expressions were assayed using immunohistochemistry. The messenger RNA (mRNA) and/or protein levels of FSIP1 in fresh bladder tumor tissues as well as bladder cancer cell lines were measured by quantitative real-time polymerase chain reaction (PCR) and Western blotting analysis. The correlation of FSIP1 expression with clinicopathological parameters was also evaluated. Western blotting analysis revealed that FSIP1 protein was detected in 94.1% (16/17) of bladder tumor specimens and in all three bladder cancer cell lines (5637, BIU-87, and T24 in particular), with significantly higher expression than those of their controls. Quantitative real-time PCR demonstrated an increased FSIP1 mRNA expression level in bladder cancer tissues than in normal adjacent tissues (P=0.012). FSIP1 overexpression showed good correlation with tumor stage and lymph node metastasis (P=0.027 and 0.000, respectively). Positive FSIP1 expression was independently associated with an unfavorable overall and disease-free survival by multivariate Cox regression (P=0.037 and 0.019, respectively). FSIP1 overexpression is associated with unfavorable prognosis in patients with bladder cancer. Thus, FSIP1 represents a potential therapeutic or predictive target for bladder cancer. Keywords: bladder cancer, fibrous sheath interacting protein 1, prognosis, survival, metastasis

Xiaoli Wang,1,2,* Yijun Luo,1,2,* Minghuan Li,2 Hongjiang Yan,2 Mingping Sun,2 Tingyong Fan2 1School of Medicine and Life Sciences, Jinan University-Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, People’s Republic of China *These authors contributed equally to this work Background: Postoperative radiotherapy has shown positive efficacy in lowering the recurrence rate and improving the survival rate for patients with esophageal squamous cell carcinoma (ESCC). However, controversies still exist about the postoperative prophylactic radiation target volume. This study was designed to analyze the patterns of recurrence and to provide a reference for determination of the postoperative radiotherapy target volume for patients with midthoracic ESCC.Patients and methods: A total of 338 patients with recurrent or metastatic midthoracic ESCC after radical surgery were retrospectively examined. The patterns of recurrence including locoregional and distant metastasis were analyzed for these patients.Results: The rates of lymph node (LN) metastasis were 28.4% supraclavicular, 77.2% upper mediastinal, 32.0% middle mediastinal, 50.0% lower mediastinal, and 19.5% abdominal LNs. In subgroup analyses, the rate of abdominal LN metastasis was significantly higher in patients with histological node-positive than that in patients with histological node-negative (P=0.033). Further analysis in patients with histological node-positive demonstrated that patients with three or more positive nodes are more prone to abdominal LN metastasis, compared with patients with one or two positive nodes (χ2=4.367, P=0.037). The length of tumor and histological differentiation were also the high-risk factors for abdominal LN metastasis.Conclusion: For midthoracic ESCC with histological node-negative, or one or two positive nodes, the supraclavicular and stations 2, 4, 5, and 7 LNs should be delineated as clinical target volume of postoperative prophylactic irradiation, and upper abdominal LNs should be excluded. While for midthoracic ESCC with three or more positive nodes, upper abdominal LNs should also be included. The length of tumor and histological differentiation should be considered comprehensively to design the clinical target volume for radiotherapy. Keywords: esophagus cancer, radiotherapy, recurrence and metastasis, clinical target volume

Jun Xing,1 Yijun Luo,1,2 Xiaoli Wang,1,2 Min Gao,1 Mingping Sun,1 Xiuping Ding,1 Tingyong Fan,1 Jinming Yu1 1Department of Radiation Oncology and Radiology, Shandong Cancer Hospital Affiliated to Shandong University, 2School of Medical and Life Sciences, Shandong Academy of Medical Sciences, University of Jinan, Jinan, People’s Republic of China Purpose: Definitive chemoradiation therapy remains the standard of care for patients with localized esophageal carcinoma who choose nonsurgical management. However, there is no consensus regarding delineation of the nodal clinical target volume (CTVn), especially for lower cervical lymph nodes. This study aimed to map the location of metastatic supraclavicular lymph nodes in thoracic esophageal carcinoma patients with supraclavicular node involvement and generate an atlas to delineate the CTVn for elective nodal radiation of esophageal squamous cell carcinoma. Patients and methods: In this study, the supraclavicular regional lymph node was further divided into four subgroups. The locations of the involved supraclavicular nodes for all patients were then transferred onto a template computed tomography (CT) image. A volume probability map was then generated with nodal volumes, and was displayed on the template CT to provide a visual impression of nodal frequencies and anatomic distribution. Results: We identified 154 supraclavicular nodal metastases based on CT image in 96 patients. Of these, 29.2% were located in group I region, 59.7% in group II region, 10.4% in group III region, and 0.7% in group IV region. Conclusion: On the basis of our study, we suggest that the appropriate radiation field of CTVn should include the group I and II regions and the CTVn exterior margin along the lateral side of the internal jugular vein may be suitable. Keywords: esophageal carcinoma, lymph node metastasis, clinical target volume, cervical lymph node

Chengyan Jin,1 Xingyi Zhang,1 Mei Sun,2 Yifan Zhang,1 Guangxin Zhang,1 Bin Wang1 1Department of Thoracic Surgery, 2Department of Pathology, The Second Affiliated Hospital of Jilin University, Changchun, People’s Republic of China Objective: Given the lack of clarity on the expression status of SRC1 protein in breast cancer, we attempted to ascertain the clinical implications of the expression of this protein in breast cancer.Methods: Samples from 312 breast cancer patients who were followed up for 5 years were analyzed in this study. The associations of SRC1 expression and clinicopathological factors with the prognosis of breast cancer were determined.Results: The 312 breast cancer patients underwent radical resection, and 155 (49.68%) of them demonstrated high expression of SRC1 protein. No significant differences were found for tumor size, estrogen receptor expression, or progesterone receptor expression (P=0.191, 0.888, or 0.163, respectively). It is noteworthy that SRC1 expression was found to be related to HER-2 and Ki-67 expression (P=0.044 and P=0.001, respectively). According to logistic regression analysis, SRC1 expression was also significantly correlated with Ki-67 and HER-2 expression (P=0.032 and P=0.001, respectively). Survival analysis showed that patients with a high expression of SRC1 and NANOG and those with SRC1 and NANOG coexpression had significantly poorer postoperative disease-specific survival than those with no expression in the HER-2-positive group (P=0.032, 0.01, and P=0.01, respectively).Conclusion: High SRC1 protein expression was related to the prognosis of HER-2-overexpressing breast cancers. Keywords: breast cancer, prognosis, molecular classification, SRC1, NANOG

Hui Zhang,1,5,* Mengyun Wang,2,5,* Tingyan Shi,2,5 Lijun Shen,1,5 Ji Zhu,1,5 Menghong Sun,3,5 Yun Deng,1,5 Liping Liang,1,5 Guichao Li,1,5 Yongxin Wu,1,5 Ming Fan,1,5 Qingyi Wei,2,4 Zhen Zhang1,5 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 3Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 4Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA; 5Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Plasminogen activator inhibitor type 1 (PAI-1) and protease-activated receptor-1 (PAR-1) are crucial mediators of the intestinal microenvironment and are involved in radiation-induced acute and chronic injury. To evaluate whether genetic polymorphisms of PAI-1 and PAR-1 were predictors of radiation-induced injury in patients with rectal cancer, we retrospectively evaluated 356 rectal cancer patients who had received pelvic radiotherapy and analyzed the association of genetic polymorphisms of PAI-1 and PAR-1 with acute toxicities after radiotherapy. Acute adverse events were scored, including dermatitis, fecal incontinence (anal toxicity), hematological toxicity, diarrhea, and vomiting. The patients were grouped into grade ≥2 and grade 0–1 toxicity groups to analyze the acute toxicities. Genotyping of six single nucleotide polymorphisms (SNPs) of PAI-1 and PAR-1 was performed using TaqMan assays. A logistic regression model was used to estimate the odds ratios and 95% confidence intervals. Of the 356 individuals, 264 (72.5%) had grade ≥2 total toxicities; within this group, there were 65 (18.3%) individuals who reached grade ≥3 toxicities. There were 19.5% (69/354) and 36.9% (130/352) patients that developed grade ≥2 toxicities for diarrhea and fecal incontinence, respectively. The variant genotype GG of rs1050955 in PAI-1 was found to be negatively associated with the risk of diarrhea and incontinence (P

Hai-Xia Fan,1 Yan Chen,1 Bo-Xiong Ni,1 Shan Wang,1 Miao Sun,2 Dong Chen,2 Jin-Hua Zheng11Department of Anatomy, Basic Medical Science College, 2Department of Oral and Maxillofacial Surgery, Stomatological Hospital, Harbin Medical University, Harbin, People’s Republic of ChinaBackground: Matrix metalloproteinase (MMP)-1 degrades type I collagen of the extracellular matrix and also activates protease activated receptor (PAR)-1 to induce angiogenesis. The aims of this study were to evaluate microvessel density (MVD) and the expression of PAR-1 and MMP-1 in oral squamous cell carcinoma (SCC) specimens with different patterns of invasion (POI) and to evaluate their association with clinical outcomes.Methods: Seventy-four surgically obtained oral SCC samples were classified by POI according to hematoxylin-eosin staining. MVD and the localization and intensity of PAR-1 and MMP-1 expression were detected by immunohistochemistry.Results: Of the 74 oral SCC samples, 18, 5, 34, and 17 showed type I, II, III, and IV POI, respectively. MVD and expression levels of MMP-1 and PAR-1 differed between POI types I–II and POI types III–IV. Patients with low tumor expression of MMP-1 and PAR-1 and low MVD had a longer survival time than those with high tumor expression of MMP-1 and PAR-1. Moreover, the survival time of patients with POI types III–IV was shorter than that of patients with POI types I–II.Conclusion: POI combined with expression levels of MMP-1 and PAR-1 may be a valuable tool for assessing the clinical prognosis of patients with oral SCC.Keywords: oral squamous cell carcinoma, pattern of invasion, immunohistochemistry, clinical outcomes

Objective: The aim of this study was to systematically investigate the safety and efficacy of the combination of transcatheter hepatic arterial chemoembolization (TACE) and cinobufotalin injection for advanced hepatocellular carcinoma (HC)., Methods: Clinical trials were searched from Web of Science, Cochrane Library, PubMed, Embase, Chinese Medical Citation Index (CMCI), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), and Wanfang database. Outcome measures including therapeutic efficacy, quality of life, liver function, immune function, and adverse events were extracted and evaluated., Results: After final assessment, 27 studies including 2,079 advanced HC patients were involved in this study. Compared with TACE alone, the combination of TACE with cinobufotalin injection adjuvant therapy significantly prolonged the patients' 1-, 1.5-, 2-, and 3-year overall survival (OS) rate (1-year OS, OR=2.84, 95% CI=2.20-3.67, P <0.00001; 1.5-year OS, OR=3.57, 95% CI=1.92-6.66, P <0.0001; 2-year OS, OR=3.17, 95% CI=2.36-4.25, P <0.00001; 3-year OS, OR=2.88, 95% CI=1.82-4.57, P <0.00001). The combined therapy also improved patients' overall response rate (ORR; OR=1.86, 95% CI=1.54-2.24, P <0.00001), disease control rate (DCR; OR=2.05, 95% CI=1.59-2.64, P <0.00001), and quality of life improved rate (QIR; OR=3.45, 95% CI=2.52-4.72, P <0.00001). Moreover, the immune function and liver function of HC patients were all significantly enhanced after the combined therapy of TACE and cinobufotalin injection (CD3 + , P =0.001; CD4 + , P =0.0006; CD4 + /CD8 + , P =0.03; natural killer [NK] cell, P =0.01; total bilirubin [TBIL], P =0.003; alanine aminotransferase [ALT], P <0.00001; aspartate aminotransferase [AST], P <0.00001). No serious adverse events occurred during cinobufotalin injection-mediated therapy., Conclusion: The combination of TACE and cinobufotalin injection adjuvant therapy is safe and more effective for end-stage HC treatment than TACE alone., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) is a unique subtype of this disease. Few studies focus on the feasibility of trastuzumab as maintenance or palliative therapy for patients with HER2-positive advanced GC., Patients and Methods: We retrospectively analyzed the data of 11 patients, evaluated the efficacy and safety of trastuzumab, and attempted to investigate the prognostic factors for trastuzumab treatment. Among the 11 patients, one achieved partial response (PR), six achieved stable disease (SD), and four were evaluated as progressive disease (PD)., Results: The overall response rate (ORR) was 9.10%, and the disease control rate (DCR) was 63.64%. The median overall survival (OS) was 6.10 months, and the median progression-free survival (PFS) was 6.10 months. A significant association was found between trastuzumab treatment cycles and efficacy ( P= 0.027), cycles and PFS ( P= 0.001), and cycles and OS ( P= 0.005). Among the five patients who accepted more than five cycles of trastuzumab, the median OS and median PFS achieved 23.83 months and 14.67 months, respectively. Moreover, we have found the correlation between tumor marker changes and efficacy ( P= 0.002) and HER2 status and PFS ( P= 0.027). No association was found between HER2 status and OS ( P= 0.597)., Conclusion: The most common adverse events were left ventricular ejection fraction (LVEF) reduction, fatigue, and anorexia. LVEF reduction was found in seven of 11 patients, but the absolute decline in the LVEF was within 10% from the baseline. The results of this study suggest that trastuzumab is a feasible option as maintenance or palliative therapy for patients with HER2-positive metastatic GC., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Multiple studies have demonstrated that lncRNAs extensively participate in human cancer proliferation and metastasis. Epigenetic modification, transcriptional and posttranscriptional regulatory mechanisms are involved in lncRNA-led tumorigenesis and transfer. Recently, a novel identified homeobox (HOX) A11 antisense lncRNA, HOXA11-AS , 1,628 bp in length, has been excessively highlighted to be an essential initiator and facilitator in the process of malignant tumor proliferation and metastasis. As found in many reports, HOXA11-AS can not only act as a molecular scaffold of PRC2, LSD1 and DNMT1 to epigenetically modify chromosomes in the nucleus but also occur as ceRNA competitively sponging miRNAs in the cytoplasm. Furthermore, HOXA11-AS may function as a potential biomarker for cancer diagnosis and prognosis. In this review, we summarize the evolvement and mechanisms of HOXA11-AS in proliferation and metastasis of various human cancers., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Objective: To study the effects of vascular endothelial growth factor C small interfering RNA and endostatin on esophageal squamous cell carcinoma-related ring formation in vitro and proliferation of lymphatic endothelial cells., Materials and Methods: KYSE150 cells were subjected to analysis of cell transfection and endostatin operation. The groups were as follows: negative group, blank group, negative plus endostatin group, endostatin group, SG1 group, SG2 group, SG1 plus endostatin group, and SG2 plus endostatin group. The esophageal cancer-related microlymphatic endothelial cells were three-dimensionally cultured. Cell Counting Kit-8 (CCK-8) assay was employed to detect cell proliferation., Results: The negative group's three-dimensional culture result was the highest, followed by the blank group, negative plus endostatin group, endostatin group, SG2 group, SG1 group, SG1 plus endostatin group, and SG2 plus endostatin group. The quantity of living cells in the blank group was the highest, followed by the negative control, endostatin, SG2, SG1, negative plus endostatin, SG1 plus endostatin, and SG2 plus endostatin groups., Conclusion: Both vascular endothelial growth factor C small interfering RNA and endostatin could inhibit ring formation in esophageal squamous cell carcinoma and proliferation of lymphatic endothelial cells., Competing Interests: The authors report no conflicts of interest in this work.

Purpose: Despite advancements in its treatment, gastric cancer continues to be one of the leading causes of cancer deaths worldwide. Adoptive transfer of chimeric antigen receptor-modified T cells is a promising antitumor therapy for many cancers. The purpose of this study was to construct a chimeric receptor linking the extracellular domain of NKG2D to the CD28 and CD3zeta chain intracellular domains to target gastric cancers that expressed NKG2D ligands., Methods: Expression of NKG2D ligands including MICA, MICB, and ULBP1-3 in a gastric cancer cell line and primary gastric cancer cells from ascites samples were analyzed using flow cytometry. Co-culture experiments were performed by incubating chNKG2D T cells with gastric cancer cell lines and with primary human gastric cancer cells isolated from ascites and by measuring cytokine and chemokine release and cytotoxicity., Results: Gastric cancer cell lines and ascites-derived primary human gastric cancer cells expressed high levels of MICA, MICB, and ULBP2. ChNKG2D T cells secreted proinflammatory cytokines and chemokines when cultured with these cancer cells. In addition, chNKG2D T cells lysed gastric cancer cell lines and the ascites-derived primary human gastric cancer cells., Conclusion: These data indicate that treatment with chNKG2D-expressing T cells is a potential immunotherapy for gastric cancer with peritoneal metastasis.