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Cancer Gene Therapy

Darshini Kuruppu, Deepak Bhere, Christian T Farrar, Khalid Shah, Anna-Liisa Brownell, Kenneth K Tanabe
Meningeal metastasis is a fatal complication of breast cancer which affects 8-15% of patients who experience severe neurological complications of cranial nerves, cerebrum, and spinal cord. Survival once diagnosed is less than 4 months. Currently there is no cure. Aggressive multimodal radiation, intra-CSF, or systemic chemotherapy is palliative. Investigation of urgently needed new treatment modalities is hindered by the lack of suitable animal models to effectively study tumor growth kinetics. We present a model of meningeal metastases where tumor growth and associated neurological symptoms have been characterized over 3 weeks by sequential molecular imaging, tumor growth kinetics, and histopathology...
November 13, 2018: Cancer Gene Therapy
Arpita De, Blake A Jacobson, Mark S Peterson, Margaret E Stelzner, Joe Jay-Dixon, Marian G Kratzke, Manish R Patel, Peter B Bitterman, Robert A Kratzke
Hyperactivation of eIF4F-mediated translation occurs in many if not all cancers. As a consequence, cancer cells aberrantly enhance expression of malignancy-related proteins that are involved in cell cycle progression, angiogenesis, growth, and proliferation. With this in mind eIF4F is a promising molecular target for therapeutics that counteract pathological eIF4F activity. Here we used 4EGI-1, a small-molecule inhibitor of cap-mediated translation that disrupts formation of the eukaryotic initiation factor 4F (eIF4F) complex to treat non-small cell lung cancer (NSCLC)...
November 12, 2018: Cancer Gene Therapy
Aya Hirata, Hisayoshi Hashimoto, Chihiro Shibasaki, Kenta Narumi, Kazunori Aoki
The effect of IFN-α on the immunosuppressive tumor microenvironment is not fully understood. We previously reported that intratumoral IFN-α gene transduction decreased the frequency of regulatory T cells (Tregs) in the tumor by inducing the secretion of IL-6 from dendritic cells. In this study, we examined whether IFN-α affects the trafficking of Tregs to the tumor. Since CT26 cells expressed CCL17 among Treg-attracting chemokines, we focused on its role in IFN-α-mediated Treg suppression. IFN-α directly suppressed CCL17 production from CT26 cells in vitro, and IFN-α transduction reduced CCL17 expression in tumors in vivo...
November 12, 2018: Cancer Gene Therapy
Hajime Nakamura, Kohichi Takada, Yohei Arihara, Naotaka Hayasaka, Kazuyuki Murase, Satoshi Iyama, Masayoshi Kobune, Koji Miyanishi, Junji Kato
The over-expression of six-transmembrane epithelial antigen of the prostate 1 (STEAP1) underlies the pathogenesis of a large subset of human cancers. Expressed on the cancer cell surface, STEAP1 is an attractive target for antibody-based therapy or immunotherapy. However, its role in modulating the pathophysiology of colorectal cancer (CRC) remains relatively unexplored. In this study, we first demonstrated that the STEAP1 transcript level was significantly higher in CRC tissues than in normal colonic tissues...
November 7, 2018: Cancer Gene Therapy
Sang-Jin Lee, Seung-Pil Shin, Seung Hee Lee, Jeong Won Kang, Myeong-Cherl Kook, In-Hoo Kim, Hark Kyun Kim
We conducted a phase 1 trial for single-dose intravenous Ad5CRT, a replication-defective adenovirus vector expressing HSVtk (herpes simplex virus thymidine kinase) modulated by a specific trans-splicing ribozyme that targets human telomerase reverse transcriptase (hTERT)-encoding RNAs. Dose-limiting toxicities (DLTs) were evaluated in 15 patients at dose levels of 0.1-2 × 1012 virus particles. Patients well tolerated study treatment. During the DLT evaluation period, none of the 15 patients developed any grade 4 toxicities or treatment discontinuation that was related to agents investigated by this trial...
November 5, 2018: Cancer Gene Therapy
Libo Sun, Huaxin Liang, Weidong Yu, Xingyi Jin
Glioma is a common malignant tumor of the central nervous system (CNS) that has no effective treatment. In this study, we report that colony-stimulating factor-1 receptor (CSF-1R) is a key mediator of malignant features in glioma via modulation of the activity of extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. In general, CSF-1R upregulation in glioma is associated with poor histologic grade and sursvival. Enforced expression of CSF-1R is sufficient to enhance cell growth, migration, invasion, and epithelial-mesenchymal transition, while CSF-1R silencing suppresses the above-described malignant phenotypes...
October 26, 2018: Cancer Gene Therapy
Lin Zhang, Ran Li, Kai Hu, Yifeng Dai, Yifan Pang, Yang Jiao, Yan Liu, Longzhen Cui, Jinlong Shi, Zhiheng Cheng, Lin Fu
Acute myeloid leukemia (AML) is a genetically and clinically heterogeneous disease. Gene mutational and expressional profile can aid the identification of different prognostic subgroups. Downstream of tyrosine kinase (DOK) proteins are a multigenic family of adaptors; some of them are key negative regulators of immune cell signaling. However, the expression and clinical implication of DOK family in AML has rarely been investigated. A total of 155 AML patients with DOK family (DOK1-7) expression data from The Cancer Genome Atlas database were enrolled in the study...
October 22, 2018: Cancer Gene Therapy
Shuji Kubo, Misato Takagi-Kimura, Masatoshi Tagawa, Noriyuki Kasahara
Retroviral replicating vectors (RRVs) have been shown to achieve efficient tumor transduction and enhanced therapeutic benefits in a variety of cancer models. In the present study, we evaluated a possible combinatorial effect of prodrug activator genes delivered by two different RRVs derived from amphotropic murine leukemia virus (AMLV) and gibbon ape leukemia virus (GALV) on human hepatocellular carcinoma Hep3B cells. Both RRVs showed efficient replicative spread in culture and can overcame superinfection resistance each other...
October 22, 2018: Cancer Gene Therapy
Nisansala Chandimali, Do Luong Huynh, Jiao Jiao Zhang, Jae Cheol Lee, Dae-Yeul Yu, Dong Kee Jeong, Taeho Kwon
Previously, we demonstrated that Prx II is important for survival of the gefitinib-resistant A549 (A549/GR) cell line, an NSCLC cell line derived by repeated exposure to gefitinib. Therefore, in this study, we used A549/GR cells to investigate the role of Prx II in GR NSCLC stemness. Initially, to explore the stemness characteristics and investigate the association of Prx II with those stemness characteristics, we successfully isolated a stem cell-like population from A549/GR cells. A549/GR CD133+ cells possessed important cancer stemness characteristics, including the abilities to undergo metastasis, angiogenesis, self-renewal, and to express stemness genes and epithelial-mesenchymal transition (EMT) markers...
October 19, 2018: Cancer Gene Therapy
Xiao Han, Jing-Jing Zhang, Zheng-Quan Han, Hai-Bin Zhang, Zi-An Wang
Platinum-based chemotherapy is currently a standard treatment strategy for patients with gastric cancer. Eventhough it has been widely shown that microRNAs (miRNAs) are involved in tumor development, whether miRNAs have a role in chemosensitivity of gastric cancer cells to platinum-based treatment remain largely undefined. In this study, a cisplatin-resistant gastric cancer cell line (SGC7901/DDP) with stable enhanced expression or knockdown of let-7b was generated. MTT and TUNEL assays were carried out to assess whether miR-let-7 is crucial for cell viability and apoptosis, respectively...
September 20, 2018: Cancer Gene Therapy
Síle A Johnson, Michael J Ormsby, Anne McIntosh, Stephen W G Tait, Karen Blyth, Daniel M Wall
This Article was originally published with one of the panels in Figure 5A inserted twice (SL-pEGFP). In Figure 5B there was also a typo. SL-LacZ should have read SL-pEGFP(-f1). Both 5A and 5B are corrected in both the PDF and HTML versions of the Article.
September 19, 2018: Cancer Gene Therapy
Ziqiang Yuan, Juliet C Gardiner, Elaine C Maggi, Asha Adem, George Zhang, Sylvia Lee, Peter Romanienko, Yi-Chieh Nancy Du, Steven K Libutti
We reported that inactivation of menin (the protein product of MEN1) increases activity of Dnmt1 and mediates DNA hypermethylation in the development of multiple endocrine neoplasia type 1 (MEN1) syndrome. We have developed a RCAS-TVA-based somatic gene transfer system that enables tissue-specific delivery of Dnmt1 to individual β-cells of the pancreas in a RIP-TVA mouse model. In the present study, we mediated Dnmt1 expression in islet β-cells in RIP-TVA mice by utilizing the RCAS-TVA system to test if the upregulation of Dnmt1 can promote β-cell proliferation...
September 7, 2018: Cancer Gene Therapy
Jian Meng, Jing-Guang Zhang, Song-Tao Du, Ning Li
To observe the curative effect of surgery combined with gene therapy on small hepatocellular carcinoma. Seventy-seven patients with small hepatocellular carcinoma (diameter < 5 cm) underwent surgical resection. The tumor located at the edge of the liver was treated by local excision or irregular hepatectomy. The tumor in the center of the liver was resected by hepatic lobectomy in order to ensure at least a 2-cm safety margin. Fifty-four patients underwent gene therapy (gene group) one or two times before operation, whereas 23 patients underwent surgery alone (control group) selected by themselves...
September 7, 2018: Cancer Gene Therapy
Ying Ye, Ya-Nan Song, Sai-Fei He, Ju-Hua Zhuang, Guo-Yu Wang, Wei Xia
To explore the mechanisms of GINS2 on cell proliferation and apoptosis in thyroid cancer (TC) cells. Expressions of GINS2 were inhibited in K1 and SW579 cells using gene interference technology. The abilities of proliferation and apoptosis, and cell cycle were determined by MTT assay and flow cytometric assay. The downstream molecules of GINS2 were searched by microarray and bioinformatics and validated by qRT-PCR and western blotting. In the in vivo study, the tumor growth was compared and the whole-body fluorescent imaging was analyzed...
September 4, 2018: Cancer Gene Therapy
Arthur Dyer, Richard Baugh, Suet Lin Chia, Sally Frost, Iris, Egon J Jacobus, Hena Khalique, Tzveta D Pokrovska, Eleanor M Scott, William K Taverner, Len W Seymour, Janet Lei
The 11th International Oncolytic Virus Conference (IOVC) was held from April 9-12, 2018 in Oxford, UK. This is part of the high-profile academic-led series of meetings that was started back in 2002 by Steve Russell and John Bell, with most of the previous meetings being held in North America (often in Banff). The conference brought together many of the major players in oncolytic virotherapy from all over the world, addressing all stages of research and development-from aspects of basic science and cellular immunology all the way through to early- and late-phase clinical trials...
September 4, 2018: Cancer Gene Therapy
Jilei Zhang, Lingxiu Zhang, Haoran Cui, Xinpei Zhang, Gaoqi Zhang, Xinrui Yang, Siyuan Yang, Zhihui Zhang, Jing Wang, Kai Hu, Jinlong Shi, Xiaoyan Ke, Lin Fu
The SMAD family (SMAD1-9) was critically important for regulating cellular process through transforming growth factor-β signaling pathway, and contributed to carcinogenesis; however, their prognostic roles in acute myeloid leukemia (AML) remained unclear. This study collected 84 de novo AML patients treated with chemotherapy and 71 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Kaplan-Meier survival estimate indicated that among SMAD1-9, high SMAD3 and SMAD7 expression were both associated with poor event-free survival (EFS) and overall survival (OS; all P < 0...
September 4, 2018: Cancer Gene Therapy
Changbao Chen, Aixian Tian, Meng Zhao, Xinlong Ma
The VHL tumor suppressor gene is frequently inactivated in several human tumors, including bone sarcomas. We previously identified that reduced expression of VHL protein is implicated in sarcomagenesis. However, the underlying biological functions of restored VHL protein expression have not been clearly elucidated in bone sarcomas. Here we initially constructed a recombinant adenovirus 5-VHL vector (Ad5-VHL) and evaluated its expression in bone sarcomas, and antitumor activity in vitro and in vivo. We found that the adenovirus-mediated increase of VHL significantly suppresses bone sarcoma cell growth, attributed to induction of apoptosis mediated by increased caspase-3 activity and modulated Bcl-2 protein family...
August 24, 2018: Cancer Gene Therapy
Biao Yang, Yan-Bin Ma, Sheng-Hua Chu
Glioblastoma multiforme (GBM) is the most common malignant tumor of the central nervous system and has a very poor prognosis. Currently, patients were treated by resection followed by radiotherapy plus concurrent temozolomide (TMZ) chemotherapy. However, many patients are resistant to TMZ-induced DNA damage because of upregulated expression of the DNA repair enzyme O6 -methylguanine-DNA methyltransferase (MGMT). In this study, upregulation of SATB1 and MGMT, and downregulation of SLC22A18 resulted in acquisition of TMZ resistance in GBM U87 cells...
August 24, 2018: Cancer Gene Therapy
Steven Libutti
In this issue we would like to thank all those listed below for taking the time to review for Cancer Gene Therapy in 2017-your generosity is much appreciated and we hope your association with the journal continues in the future.
October 2018: Cancer Gene Therapy
Síle A Johnson, Michael J Ormsby, Anne McIntosh, Stephen W G Tait, Karen Blyth, Daniel M Wall
Bacterial-mediated cancer therapy has shown great promise in in vivo tumour models with increased survival rates post-bacterial treatment. Improving efficiency of bacterial-mediated tumour regression has focused on controlling and exacerbating bacterial cytotoxicity towards tumours. One mechanism that has been used to carry this out is the process of bactofection where post-invasion, bacteria deliver plasmid-borne mammalian genes into target cells for expression. Here we utilised the cancer-targeting Salmonella Typhimurium strain, SL7207, to carry out bactofection into triple negative breast cancer MDA-MB-231 cells...
August 13, 2018: Cancer Gene Therapy
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