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Cancer Gene Therapy

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https://www.readbyqxmd.com/read/29755111/genomic-landscape-and-prognostic-analysis-of-mantle-cell-lymphoma
#1
Ping Yang, Weilong Zhang, Jing Wang, Yuanyuan Liu, Ran An, Hongmei Jing
To gain insight into the molecular pathogenesis of patients with mantle cell lymphoma (MCL), next-generation whole-exome sequencing of 16 MCL patients was performed. We identified recurrent mutations in genes that are well known to be functionally relevant in MCL, including ATM (37.5%), TP53 (31.3%), WHSC1 (31.3%), CCND1 (18.8%), NOTCH2 (6.3%), and CDKN2A (6.3%). We also identified somatic mutations in genes for which a functional role in MCL has not been previously suspected. These genes included CCDC15, APC, CDH1, S1PR1, ATRX, BRCA2, CASP8, and NOTCH3...
May 14, 2018: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29755110/endostatin-gene-therapy-delivered-by-attenuated-salmonella-typhimurium-in-murine-tumor-models
#2
Kang Liang, Qing Liu, Pei Li, Yue Han, Xiaoping Bian, Yibo Tang, Qingke Kong
Salmonella typhimurium (hereafter S. typhimurium), as Gram-negative facultative anaerobic bacteria, are good candidates for cancer therapy and delivering therapeutic antitumor agents. However, it is necessary to reduce the virulence of such bacteria and enhance their tumor-targeting ability, and their immunostimulatory ability to induce tumor cell apoptosis. In this study, we constructed a S. typhimurium mutant named S634 harboring aroA mutation and additional mutations involved in modifications of lipid A...
May 14, 2018: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29755109/regulated-intratumoral-expression-of-il-12-using-a-rheoswitch-therapeutic-system-%C3%A2-rts-%C3%A2-gene-switch-as-gene-therapy-for-the-treatment-of-glioma
#3
John A Barrett, Hongliang Cai, John Miao, Pranay D Khare, Paul Gonzalez, Jessica Dalsing-Hernandez, Geeta Sharma, Tim Chan, Laurence J N Cooper, Francois Lebel
The purpose of this study was to determine if localized delivery of IL-12 encoded by a replication-incompetent adenoviral vector engineered to express IL-12 via a RheoSwitch Therapeutic System® (RTS® ) gene switch (Ad-RTS-IL-12) administered intratumorally which is inducibly controlled by the oral activator veledimex is an effective approach for glioma therapy. Mice bearing 5-10-day-old intracranial GL-261 gliomas were intratumorally administered Ad-RTS-mIL-12 in which IL-12 protein expression is tightly controlled by the activator ligand, veledimex...
May 14, 2018: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29735994/therapeutic-activity-of-retroviral-replicating-vector-mediated-prodrug-activator-gene-therapy-for-pancreatic-cancer
#4
Kazuho Inoko, Kei Hiraoka, Akihito Inagaki, Mizuna Takahashi, Toshihiro Kushibiki, Koji Hontani, Hironobu Takano, Shoki Sato, Shintaro Takeuchi, Toru Nakamura, Takahiro Tsuchikawa, Toshiaki Shichinohe, Harry E Gruber, Douglas J Jolly, Noriyuki Kasahara, Satoshi Hirano
Toca 511, a retroviral replicating vector (RRV) encoding the yeast cytosine deaminase (yCD) prodrug activator gene, which mediates conversion of the prodrug 5-fluorocytosine (5-FC) to the anticancer drug 5-fluorouracil (5-FU), is currently being evaluated in Phase II/III clinical trials for glioma, and showing highly promising evidence of therapeutic activity. Here we evaluated RRV-mediated prodrug activator gene therapy as a new therapeutic approach for pancreatic ductal adenocarcinoma (PDAC). RRV spread rapidly and conferred significant cytotoxicity with prodrug in a panel of PDAC cells...
May 8, 2018: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29735993/recombinant-viruses-with-other-anti-cancer-therapeutics-a-step-towards-advancement-of-oncolytic-virotherapy
#5
REVIEW
Geetanjali Lal, Maitreyi S Rajala
Cancer as a disease is a multifaceted foe which sometimes succumbs to the prescribed treatment and sometimes develops resistance against various therapies. Conventional cancer therapies suffer from many limitations, the least of which is their specificity and systemic side effects. In a majority of cases, acquired mutations render the cancer cells resistant to therapy and lower the prognostic outcome. In the constant effort to devise a therapeutic moiety which can comprehensively eliminate cancer cells, oncolytic viruses provide an attractive avenue as they selectively infect and lyse cancer cells sparing normal cells from their effects...
May 8, 2018: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29720674/synergistic-antitumour-effects-of-rapamycin-and-oncolytic-reovirus
#6
Charles Comins, Guy Richard Simpson, William Rogers, Kate Relph, Kevin Harrington, Alan Melcher, Victoria Roulstone, Joan Kyula, Hardev Pandha
There are currently numerous oncolytic viruses undergoing clinical trial evaluation in cancer patients and one agent, Talimogene laherparepvec, has been approved for the treatment of malignant melanoma. This progress highlights the huge clinical potential of this treatment modality, and the focus is now combining these agents with conventional anticancer treatments or agents that enhance viral replication, and thereby oncolysis, in the tumour microenvironment. We evaluated the combination of reovirus with rapamycin in B16F10 cell, a murine model of malignant melanoma, based on potential mechanisms by which mTOR inhibitors might enhance viral oncolysis...
May 3, 2018: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29691470/crispr-cas9-genome-editing-technology-significantly-accelerated-herpes-simplex-virus-research
#7
REVIEW
Dong Wang, Xian-Wang Wang, Xiao-Chun Peng, Ying Xiang, Shi-Bao Song, Ying-Ying Wang, Lin Chen, Victoria W Xin, Yan-Ning Lyu, Jiafu Ji, Zhao-Wu Ma, Cheng-Bin Li, Hong-Wu Xin
Herpes simplex viruses (HSVs) are important pathogens and ideal for gene therapy due to its large genome size. Previous researches on HSVs were hampered because the technology to construct recombinant HSVs were based on DNA homology-dependent repair (HDR) and plaque assay, which are inefficient, laborious, and time-consuming. Fortunately, clustered regularly interspaced short palindromic repeat/CRISPR-associated protein 9 (CRISPR/Cas9) recently provided the possibility to precisely, efficiently, and rapidly edit genomes and indeed is successfully being used in HSVs...
April 25, 2018: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29681617/gene-expression-profiles-reveal-key-genes-for-early-diagnosis-and-treatment-of-adamantinomatous-craniopharyngioma
#8
Jun Yang, Ziming Hou, Changjiang Wang, Hao Wang, Hongbing Zhang
Adamantinomatous craniopharyngioma (ACP) is an aggressive brain tumor that occurs predominantly in the pediatric population. Conventional diagnosis method and standard therapy cannot treat ACPs effectively. In this paper, we aimed to identify key genes for ACP early diagnosis and treatment. Datasets GSE94349 and GSE68015 were obtained from Gene Expression Omnibus database. Consensus clustering was applied to discover the gene clusters in the expression data of GSE94349 and functional enrichment analysis was performed on gene set in each cluster...
April 23, 2018: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29593359/magnetic-nanoparticle-mediated-gene-therapy-to-induce-fas-apoptosis-pathway-in-breast-cancer
#9
Harun Basoglu, Beyza Goncu, Fahri Akbas
CD95 (Fas) is a complex integral protein that can be expressed in many cells. It induces apoptosis when interacted with its ligand CD95L (FasL). However, cancer cells are resistant to CD95-induced apoptosis because of the changes in death domain (DD) of CD95 (procaspase-8 and c-Flip). In this study, magnetic nanoparticles and lipid-based gene transfection methods were performed to provide active Fas expression in breast cancer cells. Plasmid DNA (pDNA), which can express both human Fas and GFP, was transfected to MCF-7 breast cancer cells...
March 29, 2018: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29593358/antitumor-effect-of-antibiotic-resistance-gene-free-plasmids-encoding-interleukin-12-in-canine-melanoma-model
#10
Ursa Lampreht Tratar, Spela Kos, Urska Kamensek, Maja Ota, Natasa Tozon, Gregor Sersa, Maja Cemazar
The electrotransfer of interleukin-12 (IL-12) has been demonstrated as an efficient and safe treatment for tumors in veterinary oncology. However, the plasmids used encode human or feline IL-12 and harbor the gene for antibiotic resistance. Therefore, our aim was to construct plasmids encoding canine IL-12 without the antibiotic resistance genes driven by two different promoters: constitutive and fibroblast-specific. The results obtained in vitro in different cell lines showed that following gene electrotransfer, the newly constructed plasmids had cytotoxicity and expression profiles comparable to plasmids with antibiotic resistance genes...
March 29, 2018: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29515240/t-bet-promotes-potent-antitumor-activity-of-cd4-car-t-cells
#11
Albert T Gacerez, Charles L Sentman
Chimeric antigen receptor (CAR) therapy has shown promise against B cell malignancies in the clinic. However, limited success in patients with solid tumors has prompted the development of new CAR strategies. In this study, a B7H6-specific CAR was combined with different variants of T-bet, a transcription factor that acts as the master regulator to induce a Th1 phenotype in CD4+ T cells, to create more effective CAR T cells. Skewing CD4+ CAR T cells into a Th1 improved CAR T cell functional activity while promoting a robust proinflammatory response against B7H6-expressing tumors...
March 7, 2018: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29511313/evaluation-of-foxc1-as-a-therapeutic-target-for-basal-like-breast-cancer
#12
Landon Mott, Kai Su, Daniel W Pack
Basal-like breast cancer (BLBC) is a malignant carcinoma with aggressive motility and rapid growth. Accounting for 15% of breast cancers, BLBC often exhibits a poor prognosis and tends to metastasize to the brain and lungs. Because most BLBC display a triple-negative phenotype (ER-, PR-, and HER2-), conventional cytotoxic chemotherapy remains the only treatment option despite poor success and high rate of relapse. The overexpression of the forkhead-box transcription factor C1 (FOXC1) was recently identified as a biomarker of BLBC...
March 6, 2018: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29491461/clinical-and-biological-implications-of-mutational-spectrum-in-acute-myeloid-leukemia-of-fab-subtypes-m4-and-m5
#13
Zhiheng Cheng, Kai Hu, Lei Tian, Yifeng Dai, Yifan Pang, Wei Cui, Hongmian Zhao, Tong Qin, Yu Han, Ning Hu, Li Chen, Chao Wang, Yijie Zhang, Depei Wu, Xiaoyan Ke, Jinlong Shi, Lin Fu
The mutational spectrum and molecular characteristics of acute myelomonocytic lineage leukemia, namely acute myeloid leukemia (AML) French-American-British (FAB) subtypes M4 and M5, are largely unknown. In order to explore the mutational spectrum and prognostic factors of FAB-M4 and -M5, next-generation sequencing (NGS) was performed to screen for mutated genes and fusion genes relevant to the pathogenesis of AML. Of the 63 patients enrolled in the study, 60% had more than three mutated genes. NPM1 had the highest mutation frequency, followed by DNMT3A, FLT3, NRAS, RUNX1, and TET2...
February 28, 2018: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29302045/mir-200c-inhibits-tgf-%C3%AE-induced-emt-to-restore-trastuzumab-sensitivity-by-targeting-zeb1-and-zeb2-in-gastric-cancer
#14
Xinliang Zhou, Xinyi Men, Riyang Zhao, Jing Han, Zhisong Fan, Yudong Wang, Yalei Lv, Jing Zuo, Lianmei Zhao, Meixiang Sang, Xian-De Liu, Baoen Shan
Gastric cancer is the fifth most common malignancy in the world, with Eastern Asia as one of areas with the highest incidence rates. Trastuzumab, a HER2-targeting antibody, combined with chemotherapy has been successfully employed for the gastric cancer patients with HER2 overexpression/amplification. However, trastuzumab resistance is a major problem in clinical practice. Here we observed that the trastuzumab-resistant gastric cancer cell line NCI-N87/TR expressed high levels of epithelial-mesenchymal transition factors and demonstrated increased migration and invasion capability compared with NCI-N87 cells...
January 4, 2018: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29282356/long-non-coding-rna-dleu1-predicts-poor-prognosis-of-gastric-cancer-and-contributes-to-cell-proliferation-by-epigenetically-suppressing-klf2
#15
Xiaobin Li, Zongze Li, Ziwen Liu, Jianchun Xiao, Shuting Yu, Yimin Song
Currently, accumulating documents have paid great attention to the critical role of long non-coding RNAs. The long non-coding RNAs DLEU1 has been demonstrated to be dysregulated in many solid tumors and hematological malignancies. However, the detailed descriptions about its potential roles and molecular mechanism in gastric cancer (GC) are still blurry. As for our research, it was found out that DLEU1 was observably intensified in GC tissues and cell lines. And highly expressed DLEU1 was relevant to tumor size, advanced stage of pathology and lymph node metastasis in GC patients...
December 27, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29255216/radiation-enhanced-delivery-of-plasmid-dna-to-tumors-utilizing-a-novel-pei-polyplex
#16
Oliver K Appelbe, Bieong-Kil Kim, Nick Rymut, Jianping Wang, Stephen J Kron, Yoon Yeo
The excitement surrounding the potential of gene therapy has been tempered due to the challenges that have thus far limited its successful implementation in the clinic such as issues regarding stability, transfection efficiency, and toxicity. In this study, low molecular weight linear polyethyleneimine (2.5 kDa) was modified by conjugation to a lipid, lithocholic acid, and complexed with a natural polysaccharide, dermatan sulfate (DS), to mask extra cationic charges of the modified polymer. In vitro examination revealed that these modifications improved complex stability with plasmid DNA (pDNA) and transfection efficiency...
December 19, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29255215/potential-usefulness-of-brevibacillus-for-bacterial-cancer-therapy-intratumoral-provision-of-tumor-necrosis-factor-%C3%AE-and-anticancer-effects
#17
Hidefumi Mukai, Maiko Takahashi, Yasuyoshi Watanabe
Bacterial cancer therapy, wherein bacteria are used as a gene expression system for the exogenous protein of interest in the body, has started becoming a focus area of research; therefore, studying potential bacterial species for use is extremely important. Here, we investigated the use of Brevibacillus choshinensis as an effective and safe provider of anticancer proteins in the body, using a transformant expressing murine tumor necrosis factor-α (mTNF-α). The transformant sustainably provided mTNF-α in tumors in mice for a few hours post-injection...
December 18, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29242639/development-of-an-adenovirus-vector-vaccine-platform-for-targeting-dendritic-cells
#18
Piyush K Sharma, Igor P Dmitriev, Elena A Kashentseva, Geert Raes, Lijin Li, Samuel W Kim, Zhi-Hong Lu, Jeffrey M Arbeit, Timothy P Fleming, Sergey A Kaliberov, S Peter Goedegebuure, David T Curiel, William E Gillanders
Adenoviral (Ad) vector vaccines represent one of the most promising modern vaccine platforms, and Ad vector vaccines are currently being investigated in human clinical trials for infectious disease and cancer. Our studies have shown that specific targeting of adenovirus to dendritic cells dramatically enhanced vaccine efficacy. However, this was achieved using a molecular adapter, thereby necessitating a two component vector approach. To address the mandates of clinical translation of our strategy, we here sought to accomplish the goal of DC targeting with a single-component adenovirus vector approach...
December 15, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29234154/lncrna-snhg16-predicts-poor-prognosis-and-promotes-tumor-proliferation-through-epigenetically-silencing-p21-in-bladder-cancer
#19
Xianxiang Cao, Jing Xu, Dong Yue
More and more evidences have ensured the crucial functions of long non-coding RNAs (lncRNAs) in multiple tumors. It has been discovered that lncRNA-SNHG16 is involved in many tumors. Even so, it is still necessary to study SNHG16 comprehensively in bladder cancer. In terms of our study, the level of SNHG16 both in the tumor tissues and cell lines was measured and the relationship among SNHG16, clinicopathological traits and prognosis was explored. Interference assays were applied to determine the biological functions of SNHG16...
December 12, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29234153/netrin-1-elicits-metastatic-potential-of-non-small-cell-lung-carcinoma-cell-by-enhancing-cell-invasion-migration-and-vasculogenic-mimicry-via-emt-induction
#20
Xiaofei Zhang, Ping Cui, Beichen Ding, Yuening Guo, Kaiyu Han, Jianing Li, Hong Chen, Wei Zhang
Ectopic expression of netrin-1 has been validated in several cancers including non-small cell lung cancer (NSCLC). Recent research confirms the critical role of netrin-1 in NSCLC growth and its prognostic value. Unfortunately, its contribution in NSCLC metastasis remains elusive. Here, netrin-1 had relatively high expression in NSCLC tissues and cells, especially in high metastatic groups. Notably, netrin-1 overexpression aggravated the malignant metastatic behavior of NSCLC cells, including cell invasion, migration, and vasculogenic mimicry (VM), whereas netrin-1 depression reversely dampened the metastatic potential...
December 12, 2017: Cancer Gene Therapy
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