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Sakhi H, Arabi M, Ghaemi A, Movafagh A, Sheikhpour M. Oncolytic viruses in lung cancer treatment: a review article. Immunotherapy 2024; 16:75-97. [PMID: 38112057 DOI: 10.2217/imt-2023-0124] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Accepted: 11/21/2023] [Indexed: 12/20/2023] Open
Abstract
Lung cancer has a high morbidity rate worldwide due to its resistance to therapy. So new treatment options are needed to improve the outcomes of lung cancer treatment. This study aimed to evaluate the effectiveness of oncolytic viruses (OVs) as a new type of cancer treatment. In this study, 158 articles from PubMed and Scopus from 1994 to 2022 were reviewed on the effectiveness of OVs in the treatment of lung cancer. The oncolytic properties of eight categories of OVs and their interactions with treatment options were investigated. OVs can be applied as a promising immunotherapy option, as they are reproduced selectively in different types of cancer cells, cause tumor cell lysis and trigger efficient immune responses.
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Affiliation(s)
- Hanie Sakhi
- Department of Mycobacteriology & Pulmonary Research, Pasteur Institute of Iran, Tehran, 1316943551, Iran
| | - Mohadeseh Arabi
- Department of Mycobacteriology & Pulmonary Research, Pasteur Institute of Iran, Tehran, 1316943551, Iran
| | - Amir Ghaemi
- Department of Virology, Pasteur Institute of Iran, Tehran, 1316943551, Iran
| | - Abolfazl Movafagh
- Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, 1983969411, Iran
| | - Mojgan Sheikhpour
- Department of Mycobacteriology & Pulmonary Research, Pasteur Institute of Iran, Tehran, 1316943551, Iran
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2
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Stanley R, Flanagan S, Reilly DO, Kearney E, Naidoo J, Dowling CM. Immunotherapy through the Lens of Non-Small Cell Lung Cancer. Cancers (Basel) 2023; 15:cancers15112996. [PMID: 37296957 DOI: 10.3390/cancers15112996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Revised: 05/24/2023] [Accepted: 05/28/2023] [Indexed: 06/12/2023] Open
Abstract
Immunotherapy has revolutionised anti-cancer treatment in solid organ malignancies. Specifically, the discovery of CTLA-4 followed by PD-1 in the early 2000s led to the practice-changing clinical development of immune checkpoint inhibitors (ICI). Patients with lung cancer, including both small cell (SCLC) and non-small cell lung cancer (NSCLC), benefit from the most commonly used form of immunotherapy in immune checkpoint inhibitors (ICI), resulting in increased survival and quality of life. In NSCLC, the benefit of ICIs has now extended from advanced NSCLC to earlier stages of disease, resulting in durable benefits and the even the emergence of the word 'cure' in long term responders. However, not all patients respond to immunotherapy, and few patients achieve long-term survival. Patients may also develop immune-related toxicity, a small percentage of which is associated with significant mortality and morbidity. This review article highlights the various types of immunotherapeutic strategies, their modes of action, and the practice-changing clinical trials that have led to the widespread use of immunotherapy, with a focus on ICIs in NSCLC and the current challenges associated with advancing the field of immunotherapy.
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Affiliation(s)
- Robyn Stanley
- School of Medicine, University of Limerick, V94 T9PX Limerick, Ireland
| | - Saoirse Flanagan
- School of Medicine, University of Limerick, V94 T9PX Limerick, Ireland
| | | | - Ella Kearney
- School of Medicine, University of Limerick, V94 T9PX Limerick, Ireland
| | - Jarushka Naidoo
- Beaumont Hospital, D09 V2N0 Dublin, Ireland
- Department of Medicine, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland
- Sidney Kimmel Comprehensive Cancer Centre, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Catríona M Dowling
- School of Medicine, University of Limerick, V94 T9PX Limerick, Ireland
- Department of Medicine, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland
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3
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Yang R, Liu Z, Cao H, Shi Y. LINC01089, suppressed by YY1, inhibits lung cancer progression by targeting miR-301b-3p/HPDG axis. Cell Biol Toxicol 2022; 38:1063-1077. [PMID: 34561789 DOI: 10.1007/s10565-021-09643-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Accepted: 08/09/2021] [Indexed: 01/25/2023]
Abstract
PURPOSE LINC01089 is a newly identified lncRNA and rarely reported in human cancers. Our study aimed to investigate its role in lung cancer. METHODS YY1, LINC01089, and miR-301b-3p levels in lung cancer tissues and cells were assessed using qRT-PCR. Bioinformatics analysis and luciferase reporter, ChIP, and RIP assays were carried out for determining the relationships among YY1, LINC01089, miR-301b-3p, and HPGD. Gain- and loss-of-function assays were carried out to confirm the impacts of LINC01089 and HPDG in lung cancer cells. CCK-8 assay was used to assess cell proliferation rate, and Transwell assay was applied to measure cell invasion and migration. An in vivo tumor model was applied for validating the role of LINC01089. RESULTS LINC01089 was decreased in lung cancer tissues and cells, and low LINC01089 level predicted a poor clinical outcome. YY1 directly bound to LINC01089 promoter region and inhibited its transcription. LINC01089 knockdown thwarted the proliferation, invasion, and migration capacity of H1299 and A549 cells and aggravated tumor growth. Specifically, LINC01089 functioned as a competing endogenous RNA of miR-301b-3p to modulate HPGD and thereby affected lung cancer progression. CONCLUSION Our data revealed that LINC01089, directly suppressed by YY1, inhibited lung cancer progression by targeting the miR-301b-3p/HPGD axis. Graphical abstract 1. LINC01089 expression was downregulated in lung cancer tisuues and cell lines, and low LINC01089 levels predicted a poor clinical outcome. 2. LINC01089 knockdown enhanced proliferation, invasion, and migration of H1299 and A549 cells in vitro and promoted lung cancer cell tumorigenesis and metastasis in vivo. 3. LINC01089, directly suppressed by YY1, functioned as a competing endogenous RNA against miR-301b-3p to increase HPGD expression.
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Affiliation(s)
- Rusong Yang
- Department of Thoracic Surgery, The Second Affiliated Hospital of Nanjing Medical University, No.121 Jiangjiayuan Road, Gulou District, Nanjing, Jiangsu, 210011, People's Republic of China.
| | - Zhengcheng Liu
- Department of Thoracic Surgery, The Second Affiliated Hospital of Nanjing Medical University, No.121 Jiangjiayuan Road, Gulou District, Nanjing, Jiangsu, 210011, People's Republic of China
| | - Hui Cao
- Department of Thoracic Surgery, The Second Affiliated Hospital of Nanjing Medical University, No.121 Jiangjiayuan Road, Gulou District, Nanjing, Jiangsu, 210011, People's Republic of China
| | - Ye Shi
- Department of Thoracic Surgery, The Second Affiliated Hospital of Nanjing Medical University, No.121 Jiangjiayuan Road, Gulou District, Nanjing, Jiangsu, 210011, People's Republic of China
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4
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Li H, Gao J, Zhang S. Functional and Clinical Characteristics of Cell Adhesion Molecule CADM1 in Cancer. Front Cell Dev Biol 2021; 9:714298. [PMID: 34395444 PMCID: PMC8361327 DOI: 10.3389/fcell.2021.714298] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 07/02/2021] [Indexed: 12/21/2022] Open
Abstract
The cell adhesion molecule CADM1, which participates in cell adhesion and signal transduction, has a regulatory effect on the development of tumors. CADM1 is often involved in malignant tumors of multiple organ systems, such as the respiratory and digestive systems. Upregulated CADM1 promotes tumor cell apoptosis and inhibits malignant proliferation. Along with cell cycle-related proteins, it participates in regulating signaling pathways, such as EMT, STAT3, and AKT, and plays an important role in inhibiting invasion and migration. Considering clinical characteristics, low CADM1 expression is associated with aggressive tumors and poor prognosis. In addition, some long non-coding RNAs (lncRNAs) or miRNAs directly or indirectly act on CADM1 to regulate tumor growth and motility. Interestingly, CADM1 function differs in adult T-cell leukemia/lymphoma (ATLL), and NF-κB is thought to be involved in this process. Taken together, CADM1 could be a potential biomarker for early diagnosis and a target for cancer treatment in future clinical practices.
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Affiliation(s)
- Hongxu Li
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ, Transplantation at Henan Universities, Zhengzhou, China.,Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou, China
| | - Jie Gao
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ, Transplantation at Henan Universities, Zhengzhou, China.,Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou, China
| | - Shuijun Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ, Transplantation at Henan Universities, Zhengzhou, China.,Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou, China
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Wang Y, Huang P, Hu Y, Guo K, Jia X, Huang B, Liu X, He X, Huang F. An oncolytic adenovirus delivering TSLC1 inhibits Wnt signaling pathway and tumor growth in SMMC-7721 xenograft mice model. Acta Biochim Biophys Sin (Shanghai) 2021; 53:766-774. [PMID: 33928346 DOI: 10.1093/abbs/gmab048] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Indexed: 11/13/2022] Open
Abstract
Tumor suppressor in lung cancer-1 (TSLC1) was first identified as a tumor suppressor for lung cancer, and frequently downregulated in various types of cancers including hepatocellular carcinoma (HCC). The Wnt pathway plays a critical role in tumorigenesis, migration, and invasion in HCC. However, the function of TSLC1 in modulating Wnt signaling in HCC is unclear. In this study, we evaluated the effect of TSLC1-armed oncolytic adenovirus (S24-TSLC1) on the Wnt/β-catenin pathway, cell viability, invasion and migration abilities of HCC in vitro and the growth of SMMC-7721-xenografted tumor in mice model. We detected the expression of TSLC1 in tumor samples and HCC cell lines. The results showed that TSLC1 expression was low in HCC, but high in pericarcinomatous tissue and normal cells, which implied that TSLC1 is a tumor suppressor of liver cancer. S24-TSLC1 exhibited an antitumor effect on HCC cell growth in vitro, but did little damage to normal liver cells. Overexpression of TSLC1 downregulated the transcriptional activity of TCF4/β-catenin and inhibited the mRNA or protein expression of Wnt target genes cyclinD1 and c-myc. S24-TSLC1 also inhibited the invasion and migration of HCC cells. Animal experiments further confirmed that S24-TSLC1 significantly inhibited tumor growth of the SMMC-7721-xenografted tumor. In conclusion, TSLC1 could downregulate the Wnt signal pathway and suppress HCC cell growth, migration and invasion, suggesting that S24-TSLC1 may be a potent antitumor agent for future clinical trials in liver cancer treatment.
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Affiliation(s)
- Yigang Wang
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China
| | - Panpan Huang
- School of Basic Medicine, Gannan Medical University, Ganzhou 341000, China
| | - Yanping Hu
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China
| | - Keni Guo
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China
| | - Xiaoyuan Jia
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China
| | - Biao Huang
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China
| | - Xinyuan Liu
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China
- State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
| | - Xianglei He
- Department of Pathology, Zhejiang Provincial People’s Hospital, Hangzhou 311402, China
| | - Fang Huang
- Department of Pathology, Zhejiang Provincial People’s Hospital, Hangzhou 311402, China
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Freda CT, Yin W, Ghebrehiwet B, Rubenstein DA. SARS-CoV-2 proteins regulate inflammatory, thrombotic and diabetic responses in human arterial fibroblasts. Clin Immunol 2021; 227:108733. [PMID: 33895357 PMCID: PMC8061629 DOI: 10.1016/j.clim.2021.108733] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 04/19/2021] [Accepted: 04/20/2021] [Indexed: 12/21/2022]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for many pathological processes, including altered vascular disease development, dysfunctional thrombosis and a heightened inflammatory response. However, there is limited work to determine the underlying cellular responses induced by exposure to SARS-CoV-2 structural proteins. Thus, our objective was to investigate how human arterial adventitial fibroblasts inflammation, thrombosis and diabetic disease markers are altered in response to Spike, Nucleocapsid and Membrane-Envelope proteins. We hypothesized that after a short-term exposure to SARS-CoV-2 proteins, adventitial fibroblasts would have a higher expression of inflammatory, thrombotic and diabetic proteins, which would support a mechanism for altered vascular disease progression. After incubation, the expression of gC1qR, ICAM-1, tissue factor, RAGE and GLUT-4 was significantly up-regulated. In general, the extent of expression was different for each SARS-CoV-2 protein, suggesting that SARS-CoV-2 proteins interact with cells through different mechanisms. Thus, SARS-CoV-2 protein interaction with vascular cells may regulate vascular disease responses.
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Affiliation(s)
- Christopher Thor Freda
- Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, United States of America
| | - Wei Yin
- Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, United States of America
| | - Berhane Ghebrehiwet
- Department of Medicine, Stony Brook University, Stony Brook, NY 11794, United States of America
| | - David A Rubenstein
- Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, United States of America.
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Zhang Y, Ye M, Huang F, Wang S, Wang H, Mou X, Wang Y. Oncolytic Adenovirus Expressing ST13 Increases Antitumor Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Against Pancreatic Ductal Adenocarcinoma. Hum Gene Ther 2020; 31:891-903. [PMID: 32475172 DOI: 10.1089/hum.2020.024] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Oncolytic adenoviruses (OAds) are promising agents for cancer therapy, representing a novel therapeutic strategy for pancreatic ductal adenocarcinoma (PDAC). However, there are challenges associated with the successful use of an OAd alone, involving the security of the viral vector and screening of an effective antitumor gene. In the present study, a novel OAd CD55-ST13-tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was constructed in which the dual therapeutic genes ST13 and TRAIL were inserted, featuring the carcinoembryonic antigen (CEA) as a promoter to control E1A and deletion of the 55 kDa E1B gene. ST13, known as a colorectal cancer suppressor gene, exhibited lower expression in PDAC than in tumor-adjacent tissues and was associated with poor prognosis in PDAC patients. In vitro studies demonstrated that CD55-ST13-TRAIL was effective in promoting the expression of ST13 and TRAIL in CEA-positive pancreatic cancer cells. Moreover, CD55-ST13-TRAIL exhibited a synergistic effect toward tumor cell death compared with CD55-ST13 alone or CD55-TRAIL alone, and inhibited tumor cell proliferation and induced cell apoptosis dependent on caspase pathways in PDAC cells. Furthermore, xenograft experiments in a mouse model indicated that CD55-ST13-TRAIL significantly inhibited tumor growth and improved the survival of animals with xenografts. The findings demonstrate that oncolytic virotherapy under the control of the promoter CEA enables safe and efficient treatment of PDAC, and suggest that it represents a promising candidate for the treatment of metastatic diseases.
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Affiliation(s)
- Youni Zhang
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, P.R. China
| | - Miaojuan Ye
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, P.R. China
| | - Fang Huang
- Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou, P.R. China
| | - Shibing Wang
- Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, P.R. China
| | - Huiju Wang
- Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, P.R. China
| | - Xiaozhou Mou
- Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, P.R. China
| | - Yigang Wang
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, P.R. China
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8
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Guan Y, Wang Y, Bhandari A, Xia E, Wang O. IGSF1: A novel oncogene regulates the thyroid cancer progression. Cell Biochem Funct 2019; 37:516-524. [PMID: 31343762 DOI: 10.1002/cbf.3426] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Accepted: 07/02/2019] [Indexed: 11/10/2022]
Abstract
Thyroid cancer has been continuously increasing and extraordinarily prevalent worldwide. The genetic diagnosis has been widely used in fine needle aspiration. IGSF1, an immunoglobulin superfamily member 1, has been shown to be associated with the regulation of thyroid hormone. But the function of IGSF1 in thyroid cancer has not been explored yet. In this article, we will illuminate the correlation between IGSF1 expression and thyroid cancer. We analysed the level of IGSF1 expression in 55 pairs of tissue samples by real-time polymerase chain reaction (PCR) and The Cancer Genome Atlas (TCGA) data portal. After that, we transfected small interfering RNA to silence IGSF1 in thyroid cancer cell lines (KTC-1 and BCPAP) and confirmed the function of IGSF1 by performed colony formation, migration, invasion, cell counting kit-8, and apoptosis assays. IGSF1 was upregulated in thyroid cancer tissues compared with the adjacent normal tissues (t = 5.783, df = 54; P < .0001) and TCGA (T: N = 65.91 ± 3.998, n = 501: 2.824 ± 0.273, n = 58; P < .0001). In thyroid cell lines, experiments showed that downregulated IGSF1 inhibited proliferation, metastasis, and promoted cell apoptosis. Meanwhile, inhibited IGSF1 expression could downregulate N-cadherin, vimentin, and EZH2, which is associated with metastasis. Thyroid cancer cells IGSF1 expression levels are a correlation with its ability to growth, metastasis, and apoptosis.
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Affiliation(s)
- Yaoyao Guan
- Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
| | - Yinghao Wang
- Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
| | - Adheesh Bhandari
- Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
| | - Erjie Xia
- Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
| | - Ouchen Wang
- Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
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Zhu L, Li T, Shen Y, Yu X, Xiao B, Guo J. Using tRNA halves as novel biomarkers for the diagnosis of gastric cancer. Cancer Biomark 2019; 25:169-176. [DOI: 10.3233/cbm-182184] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Linwen Zhu
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, China
| | - Tianwen Li
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, China
| | - Yijing Shen
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, China
| | - Xiuchong Yu
- Department of Gastrointestinal Surgery, Ningbo No. 1 Hospital and the Affiliated Hospital of Medical School of Ningbo University, Ningbo, Zhejiang 315010, China
| | - Bingxiu Xiao
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, China
| | - Junming Guo
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, China
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Wang Y, Wang B, Liang J, Cui C, Ying C, Huang F, Ma B, Zhou X, Chu L. Oncolytic viro-chemotherapy exhibits antitumor effect in laryngeal squamous cell carcinoma cells and mouse xenografts. Cancer Manag Res 2019; 11:3285-3294. [PMID: 31114365 PMCID: PMC6489678 DOI: 10.2147/cmar.s196304] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Accepted: 03/17/2019] [Indexed: 01/01/2023] Open
Abstract
Background: Oncolytic virus can specifically replicate in and then lyse tumor cells, but seldom in normal cells. Further studies have shown the significant therapeutic effect of oncolytic virotherapy combining with other strategies, such as chemo-, radio-, and immunotherapy et al. In this study, we investigated the combinational effect of oncolytic virus ZD55-TRAIL and chemotherapy drug doxorubicin (DOX) on human laryngeal squamous cell carcinoma (LSCC). Methods: The effect of ZD55-TRAIL combined with DOX on cell growth was assessed in LSCC Hep2 cells and normal cells by MTT assay. Hochest 33342 staining was performed to observe cell morphological changes. Western blot was used to detect the expression of apoptotic activation proteins. The in vivo antitumor efficacy of combination treatment was estimated in laryngeal cancer xenograft models. Results: The combination of ZD55-TRAIL and DOX exhibited enhanced inhibitory effects on laryngocarcinoma cell growth, and had few side effects to normal cells in vitro. Chemotherapy drug increased the inducement of tumor cell apoptosis mediated by oncolytic virus. In vivo experiment confirmed that the combination treatment significantly inhibited Hep2 laryngocarcinoma xenografts growth in mice. Conclusion: The oncolytic viro-chemotherapy is a potent therapeutic approach for in vitro cytotoxicity evaluation of Hep2 cells and xenograft growth in vivo.
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Affiliation(s)
- Yigang Wang
- College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, People's Republic of China
| | - Binrong Wang
- College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, People's Republic of China
| | - Junnan Liang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China
| | - Caixia Cui
- Department of Otorhinolaryngology, Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, People's Republic of China
| | - Chang Ying
- College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, People's Republic of China
| | - Fang Huang
- Department of Pathology, Zhejiang Provincal People's Hospital, Hangzhou 310014, People's Republic of China
| | - Buyun Ma
- College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, People's Republic of China
| | - Xiumei Zhou
- College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, People's Republic of China
| | - Liang Chu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China
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11
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Chen Y, Liu L, Guo Z, Wang Y, Yang Y, Liu X. Lost expression of cell adhesion molecule 1 is associated with bladder cancer progression and recurrence and its overexpression inhibited tumor cell malignant behaviors. Oncol Lett 2018; 17:2047-2056. [PMID: 30719104 PMCID: PMC6350208 DOI: 10.3892/ol.2018.9845] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2015] [Accepted: 03/17/2017] [Indexed: 02/06/2023] Open
Abstract
Cell adhesion molecule 1 (CADM1) regulates cell-cell adhesion and an altered expression level is associated with tumorigenesis and progression. The present study assessed CADM1 expression level in 84 bladder tissues to investigate the association with clinicopathological parameters from bladder cancer patients and then investigated the effects of CADM1 overexpression on T24 bladder cancer cells in vitro. The results demonstrated that expression level of CADM1 protein was significantly reduced in bladder cancer tissues (0.26±0.14) compared with in normal bladder mucosa (0.69±0.092; P<0.01), and methylation of CADM1 promoter was responsible for silencing of CADM1 protein expression and significantly associated with tumor size, recurrence, pathology classification and clinical stage (P<0.05). Overexpression of CADM1 protein inhibited tumor cell proliferation, reduced tumor cell invasion capacity and induced tumor cell apoptosis in vitro. At the gene level, CADM1 expression level upregulated caspase-3 activity and expression of Bax and p27 protein and downregulated levels of B cell lymphoma-2, cyclinD1, cyclinE1 and cyclin dependent kinase 2 proteins. Furthermore, overexpression of CADM1 regulated the expression level of epithelial to mesenchymal transition markers, including increased expression level of E-cadherin and β-catenin, whereas it decreased the levels of Vimentin. The present study demonstrated that lost expression of CADM1 protein may exert an essential role in the development and progression of bladder cancer and suggested that CADM1 may be a novel molecular target for the control of this disease in clinical practice.
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Affiliation(s)
- Yegang Chen
- Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.,Tianjin Institute of Urology, Tianjin 300211, P.R. China
| | - Li Liu
- Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.,Tianjin Institute of Urology, Tianjin 300211, P.R. China
| | - Zhanjun Guo
- Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.,Tianjin Institute of Urology, Tianjin 300211, P.R. China
| | - Yi Wang
- Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.,Tianjin Institute of Urology, Tianjin 300211, P.R. China
| | - Yongjiao Yang
- Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.,Tianjin Institute of Urology, Tianjin 300211, P.R. China
| | - Xiaoqiang Liu
- Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.,Tianjin Institute of Urology, Tianjin 300211, P.R. China
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12
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Xiao B, Qin Y, Ying C, Ma B, Wang B, Long F, Wang R, Fang L, Wang Y. Combination of oncolytic adenovirus and luteolin exerts synergistic antitumor effects in colorectal cancer cells and a mouse model. Mol Med Rep 2017; 16:9375-9382. [PMID: 29039580 PMCID: PMC5779991 DOI: 10.3892/mmr.2017.7784] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Accepted: 08/18/2017] [Indexed: 12/13/2022] Open
Abstract
In recent years, oncolytic viruses have attracted increasing interest due to their potent antitumor effects. Luteolin, a natural product, has additionally been observed to exhibit various pharmacological antitumor activities. Previously, a novel dual-targeting oncolytic adenovirus, complement decay-accelerating factor (CD55)-tumor necrosis factor ligand superfamily member 10 (TRAIL), was constructed, which exhibited significant growth inhibitory effects in various types of tumor cell. The present study investigated whether the combination of luteolin and CD55-TRAIL was able to exert a synergistic antitumor effect in colorectal carcinoma (CRC) cells. The cytotoxicity and tumor cell apoptosis mediated by combination treatment in CRC cells were detected via an MTT assay, Hoechst staining and western blotting, respectively. Tumor growth in vivo was examined in a CRC mouse xenograft model following various treatments. The results demonstrated that the addition of luteolin enhanced oncolytic adenovirus-mediated enhanced green fluorescent protein, early region 1A and TRAIL expression. The combination of CD55-TRAIL with luteolin synergistically inhibited tumor growth and promoted CRC cellular apoptosis in vitro and in vivo. Additionally, the combination of CD55-TRAIL with luteolin significantly decreased cytotoxicity in lung/bronchial normal epithelial cells, compared with single treatment. Therefore, the combination of CD55-TRAIL with luteolin may be a novel efficient therapeutic strategy for CRC in the future.
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Affiliation(s)
- Boduan Xiao
- Xinyuan Institute of Medicine and Biotechnology, Zhejiang Sci‑Tech University, Hangzhou, Zhejiang 310018, P.R. China
| | - Yun Qin
- Xinyuan Institute of Medicine and Biotechnology, Zhejiang Sci‑Tech University, Hangzhou, Zhejiang 310018, P.R. China
| | - Chang Ying
- Xinyuan Institute of Medicine and Biotechnology, Zhejiang Sci‑Tech University, Hangzhou, Zhejiang 310018, P.R. China
| | - Buyun Ma
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam 3015 CE, The Netherlands
| | - Binrong Wang
- Xinyuan Institute of Medicine and Biotechnology, Zhejiang Sci‑Tech University, Hangzhou, Zhejiang 310018, P.R. China
| | - Fei Long
- Xinyuan Institute of Medicine and Biotechnology, Zhejiang Sci‑Tech University, Hangzhou, Zhejiang 310018, P.R. China
| | - Ruwei Wang
- Zhejiang Conba Pharmaceutical Co., Ltd., Hangzhou, Zhejiang 310018, P.R. China
| | - Ling Fang
- Zhejiang Conba Pharmaceutical Co., Ltd., Hangzhou, Zhejiang 310018, P.R. China
| | - Yigang Wang
- Xinyuan Institute of Medicine and Biotechnology, Zhejiang Sci‑Tech University, Hangzhou, Zhejiang 310018, P.R. China
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13
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Ge Y, Lei W, Ma Y, Wang Y, Wei B, Chen X, Ru G, He X, Mou X, Wang S. Synergistic antitumor effects of CDK inhibitor SNS‑032 and an oncolytic adenovirus co‑expressing TRAIL and Smac in pancreatic cancer. Mol Med Rep 2017; 15:3521-3528. [PMID: 28440486 PMCID: PMC5436152 DOI: 10.3892/mmr.2017.6472] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2015] [Accepted: 02/07/2017] [Indexed: 12/19/2022] Open
Abstract
Gene therapy using oncolytic adenoviruses is a novel approach for human cancer therapeutics. The current study aimed to investigate whether the combined use of an adenovirus expressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and second mitochondria-derived activator of caspase (Smac) upon caspase activation (ZD55-TRAIL-IETD-Smac) and cyclin-dependent kinase (CDK) inhibitor SNS-032 will synergistically reinforce their anti-pancreatic cancer activities. The experiments in vitro demonstrated that SNS-032 enhances ZD55-TRAIL-IETD-Smac-induced apoptosis and causes marked pancreatic cancer cell death. Western blot assays suggested that the SNS-032 intensified ZD55-TRAIL-IETD-Smac-induced apoptosis of pancreatic cancer cells by affecting anti-apoptotic signaling elements, including CDK-2, CDK-9, Mcl-1 and XIAP. Additionally, animal experiments further confirmed that the combination of SNS-032 and ZD55-TRAIL-IETD-Smac significantly inhibited the growth of BxPC-3 pancreatic tumor xenografts. In conclusion, the present study demonstrated that SNS-032 sensitizes human pancreatic cancer cells to ZD55-TRAIL-IETD-Smac-induced cell death in vitro and in vivo. These findings indicate that combined treatment with SNS-032 and ZD55-TRAIL-IETD-Smac could represent a rational approach for anti-pancreatic cancer therapy.
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Affiliation(s)
- Yun Ge
- Xinyuan Institute of Medicine and Biotechnology, College of Life Sciences, Zhejiang Sci‑Tech University, Hangzhou, Zhejiang 310018, P.R. China
| | - Wen Lei
- Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Yingyu Ma
- Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China
| | - Yigang Wang
- Xinyuan Institute of Medicine and Biotechnology, College of Life Sciences, Zhejiang Sci‑Tech University, Hangzhou, Zhejiang 310018, P.R. China
| | - Buyun Wei
- Xinyuan Institute of Medicine and Biotechnology, College of Life Sciences, Zhejiang Sci‑Tech University, Hangzhou, Zhejiang 310018, P.R. China
| | - Xiaoyi Chen
- Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China
| | - Guoqing Ru
- Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China
| | - Xianglei He
- Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China
| | - Xiaozhou Mou
- Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China
| | - Shibing Wang
- Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China
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14
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Huang F, Wang BR, Wu YQ, Wang FC, Zhang J, Wang YG. Oncolytic viruses against cancer stem cells: A promising approach for gastrointestinal cancer. World J Gastroenterol 2016; 22:7999-8009. [PMID: 27672294 PMCID: PMC5028813 DOI: 10.3748/wjg.v22.i35.7999] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Revised: 07/12/2016] [Accepted: 08/10/2016] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal cancer has been one of the five most commonly diagnosed and leading causes of cancer mortality over the past few decades. Great progress in traditional therapies has been made, which prolonged survival in patients with early cancer, yet tumor relapse and drug resistance still occurred, which is explained by the cancer stem cell (CSC) theory. Oncolytic virotherapy has attracted increasing interest in cancer because of its ability to infect and lyse CSCs. This paper reviews the basic knowledge, CSC markers and therapeutics of gastrointestinal cancer (liver, gastric, colon and pancreatic cancer), as well as research advances and possible molecular mechanisms of various oncolytic viruses against gastrointestinal CSCs. This paper also summarizes the existing obstacles to oncolytic virotherapy and proposes several alternative suggestions to overcome the therapeutic limitations.
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15
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Prisco AR, Hoffmann BR, Kaczorowski CC, McDermott-Roe C, Stodola TJ, Exner EC, Greene AS. Tumor Necrosis Factor α Regulates Endothelial Progenitor Cell Migration via CADM1 and NF-kB. Stem Cells 2016; 34:1922-33. [PMID: 26867147 PMCID: PMC4931961 DOI: 10.1002/stem.2339] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2015] [Accepted: 01/28/2016] [Indexed: 02/06/2023]
Abstract
Shortly after the discovery of endothelial progenitor cells (EPCs) in 1997, many clinical trials were conducted using EPCs as a cellular based therapy with the goal of restoring damaged organ function by inducing growth of new blood vessels (angiogenesis). Results were disappointing, largely because the cellular and molecular mechanisms of EPC-induced angiogenesis were not clearly understood. Following injection, EPCs must migrate to the target tissue and engraft prior to induction of angiogenesis. In this study EPC migration was investigated in response to tumor necrosis factor α (TNFα), a pro-inflammatory cytokine, to test the hypothesis that organ damage observed in ischemic diseases induces an inflammatory signal that is important for EPC homing. In this study, EPC migration and incorporation were modeled in vitro using a coculture assay where TNFα treated EPCs were tracked while migrating toward vessel-like structures. It was found that TNFα treatment of EPCs increased migration and incorporation into vessel-like structures. Using a combination of genomic and proteomic approaches, NF-kB mediated upregulation of CADM1 was identified as a mechanism of TNFα induced migration. Inhibition of NF-kB or CADM1 significantly decreased migration of EPCs in vitro suggesting a role for TNFα signaling in EPC homing during tissue repair. Stem Cells 2016;34:1922-1933.
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Affiliation(s)
- Anthony R. Prisco
- Medical College of Wisconsin, Department of Physiology, Milwaukee, WI
- Medical College of Wisconsin, Biotechnology and Bioengineering Center, Milwaukee, WI
| | - Brian R. Hoffmann
- Medical College of Wisconsin, Biotechnology and Bioengineering Center, Milwaukee, WI
- Medical College of Wisconsin, Department of Medicine, Division of Cardiology, Cardiovascular Center, Milwaukee, WI
| | - Catherine C. Kaczorowski
- University of Tennessee Health Science Center, Department of Anatomy and Neurobiology, Memphis, TN
| | - Chris McDermott-Roe
- Medical College of Wisconsin, Department of Physiology, Milwaukee, WI
- Medical College of Wisconsin, Human and Molecular Genetics Center, Milwaukee, WI
| | - Timothy J. Stodola
- Medical College of Wisconsin, Department of Physiology, Milwaukee, WI
- Medical College of Wisconsin, Biotechnology and Bioengineering Center, Milwaukee, WI
| | - Eric C. Exner
- Medical College of Wisconsin, Department of Physiology, Milwaukee, WI
- Medical College of Wisconsin, Biotechnology and Bioengineering Center, Milwaukee, WI
| | - Andrew S. Greene
- Medical College of Wisconsin, Department of Physiology, Milwaukee, WI
- Medical College of Wisconsin, Biotechnology and Bioengineering Center, Milwaukee, WI
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16
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Zhang R, Zhang X, Ma B, Xiao B, Huang F, Huang P, Ying C, Liu T, Wang Y. Enhanced antitumor effect of combining TRAIL and MnSOD mediated by CEA-controlled oncolytic adenovirus in lung cancer. Cancer Gene Ther 2016; 23:168-77. [PMID: 27080225 DOI: 10.1038/cgt.2016.11] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2015] [Revised: 02/14/2016] [Accepted: 02/16/2016] [Indexed: 12/17/2022]
Abstract
Lung cancer, especially adenocarcinoma, is one of the leading causes of death in the world. Carcinoembryonic antigen (CEA), a superb non-small-cell lung cancer marker candidate, showed a beneficial effect in cancer therapy with oncolytic adenovirus in recent studies. Cancer-targeting dual gene-virotherapy delivers two therapeutic genes, linked by a connexon, in the replication-deficient vector instead of one gene so that they can work in common. In this study, we constructed a tumor-specific oncolytic adenovirus, CD55-TRAIL-IETD-MnSOD. The virus has the fusion protein complementary DNAs for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and for manganese superoxide dismutase (MnSOD) complementary DNA linked through a 4-amino acid caspase-8 cleavage site (IETD), and uses a CEA promoter to control virus E1A express. This is the first work to use a CEA promoter-regulated oncolytic adenovirus carrying two therapeutic genes for cancer research. Its targeting and anticancer capacity was evaluated by in vitro and in vivo experiments. The results indicated that CD55-TRAIL-IETD-MnSOD caused more cell apoptosis than CD55-TRAIL or CD55-MnSOD alone, or their combination in vitro, with low cytotoxicity of normal cells. In the A549 tumor xenograft model in nude mice, data showed that CD55-TRAIL-IETD-MnSOD could effectively suppress tumor growth than single gene groups, with no histological damage in liver, spleen or kidney tissues. Thus, the CEA-regulated dual-gene oncolytic virus CD55-TRAIL-IETD-MnSOD may be a novel potential therapy for lung cancer.
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Affiliation(s)
- R Zhang
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, People's Republic of China
| | - X Zhang
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, People's Republic of China
| | - B Ma
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, People's Republic of China.,Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - B Xiao
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, People's Republic of China
| | - F Huang
- School of Public health, Zhejiang University, Hangzhou, People's Republic of China
| | - P Huang
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, People's Republic of China
| | - C Ying
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, People's Republic of China
| | - T Liu
- Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China
| | - Y Wang
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, People's Republic of China
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17
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Wang YG, Huang PP, Zhang R, Ma BY, Zhou XM, Sun YF. Targeting adeno-associated virus and adenoviral gene therapy for hepatocellular carcinoma. World J Gastroenterol 2016; 22:326-337. [PMID: 26755879 PMCID: PMC4698495 DOI: 10.3748/wjg.v22.i1.326] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Revised: 09/14/2015] [Accepted: 09/30/2015] [Indexed: 02/06/2023] Open
Abstract
Human hepatocellular carcinoma (HCC) heavily endangers human heath worldwide. HCC is one of most frequent cancers in China because patients with liver disease, such as chronic hepatitis, have the highest cancer susceptibility. Traditional therapeutic approaches have limited efficacy in advanced liver cancer, and novel strategies are urgently needed to improve the limited treatment options for HCC. This review summarizes the basic knowledge, current advances, and future challenges and prospects of adeno-associated virus (AAV) and adenoviruses as vectors for gene therapy of HCC. This paper also reviews the clinical trials of gene therapy using adenovirus vectors, immunotherapy, toxicity and immunological barriers for AAV and adenoviruses, and proposes several alternative strategies to overcome the therapeutic barriers to using AAV and adenoviruses as vectors.
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18
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Wang Y, Liu T, Huang P, Zhao H, Zhang R, Ma B, Chen K, Huang F, Zhou X, Cui C, Liu X. A novel Golgi protein (GOLPH2)-regulated oncolytic adenovirus exhibits potent antitumor efficacy in hepatocellular carcinoma. Oncotarget 2015; 6:13564-78. [PMID: 25980438 PMCID: PMC4537034 DOI: 10.18632/oncotarget.3769] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2015] [Accepted: 04/10/2015] [Indexed: 12/16/2022] Open
Abstract
Golgi apparatus is the organelle mainly functioning as protein processing and secretion. GOLPH2 is a resident Golgi glycoprotein, usually called GP73. Recent data displayed that GOLPH2 is a superb hepatocellular carcinoma (HCC) marker candidate, and even its specificity is better than liver cancer marker AFP. Oncolytic adenoviruses are broadly used for targeting cancer therapy due to their selective tumor-killing effect. However, it was reported that traditionally oncolytic adenovirus lack the HCC specificity. In this study, a novel dual-regulated oncolytic adenovirus GD55 targeting HCC was first constructed based on our cancer targeted gene-viral therapeutic strategy. To verify the targeting and effectiveness of GOLPH2-regulated oncolytic adenovirus GD55 in HCC, the anticancer capacity was investigated in HCC cell lines and animal model. The results proved that the novel GOLPH2-regulated GD55 conferred higher adenovirus replication and infectivity for liver cancer cells than oncolytic adenovirus ZD55. The GOLPH2-regulated GD55 exerted a significant grow-suppressing effect on HCC cells in vitro but little damage to normal liver cells. In animal experiment, antitumor effect of GD55 was more effective in HCC xenograft of nude mice than that of ZD55. Thus GOLPH2-regulated GD55 may be a promising oncolytic virus agent for future liver cancer treatment.
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Affiliation(s)
- Yigang Wang
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, PR China
| | - Tao Liu
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, PR China
| | - Panpan Huang
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, PR China
| | - Hongfang Zhao
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, PR China
| | - Rong Zhang
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, PR China
| | - Buyun Ma
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, PR China
| | - Kan Chen
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, PR China
| | - Fang Huang
- School of Public Health, Zhejiang University, Hangzhou 310058, PR China
| | - Xiumei Zhou
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, PR China
| | - Caixia Cui
- Otorhinolaryngology Head and Neck Surgery, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, PR China
| | - Xinyuan Liu
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, PR China.,Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China
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19
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Liu D, Feng X, Wu X, Li Z, Wang W, Tao Y, Xia Y. Tumor suppressor in lung cancer 1 (TSLC1), a novel tumor suppressor gene, is implicated in the regulation of proliferation, invasion, cell cycle, apoptosis, and tumorigenicity in cutaneous squamous cell carcinoma. Tumour Biol 2013; 34:3773-83. [PMID: 23812766 DOI: 10.1007/s13277-013-0961-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2013] [Accepted: 06/19/2013] [Indexed: 01/15/2023] Open
Abstract
Tumor suppressor in lung cancer 1 (TSLC1) is tightly implicated in a variety of biological processes and plays critical roles in tumor development and progression. However, the roles of TSLC1 in cutaneous squamous cell carcinoma (CSCC) remain to be unraveled. Here, we reported the TSLC1 gene that was significantly downregulated in CSCC tissues and cells, and survival times of patients with TSLC1 at a low level were markedly lower than that at a high level (P = 0.0070). A stepwise investigation demonstrated that an elevated TSLC1 level evoked obvious proliferation and invasion inhibitions and arrested cell cycle at G0/G1 phase in A431 cells. Moreover, increase of caspase-3 activity mediated by elevated TSLC1 level induced cell apoptosis in A431 cells. Most notably, upregulation of TSLC1 expression reduced the numbers of colony formation and tumorigenicity. Collectively, our results presented herein suggest that TSLC1 as tumor suppressor may play prominent roles in development and progression of CSCC via regulation of different biological processes.
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Affiliation(s)
- Dong Liu
- Department of Dermatology, the First Affiliated Hospital of Xinxiang Medical University, No. 88, Health Road, Weihui, Henan, 453100, China
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