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Cancer Gene Therapy

Liang Mao, Xue Li, Shu Gong, Haiyang Yuan, Yu Jiang, Wenjun Huang, Xingwang Sun, Xitong Dang
Esophageal cancer related gene-4 (Ecrg4) has been shown to be a tumor suppressor in many organs. Exosomes are naturally secreted nanosized particles that carry signal molecules including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and messenger RNAs (mRNAs) among others. Upon internalization, exosomes unload their cargos that in turn modulate the biology of the recipient cells. Mounting evidence has shown that exosomal miRNAs are functional. However, reports that exosomes carry functional mRNAs remain scarce...
July 9, 2018: Cancer Gene Therapy
Nobuaki Fujiwara, Hiroto Izumi, Yasuo Morimoto, Kazuo Sakurai, Shinichi Mochizuki
Antisense oligonucleotides (AS-ODNs) hybridize with specific mRNAs, resulting in interference with the splicing mechanism or the regulation of protein translation. We previously demonstrated that the β-glucan schizophyllan (SPG) can form a complex with AS-ODNs with attached dA40 (AS-ODNs/SPG), and this complex can be incorporated into cells, such as macrophages and dendritic cells, expressing the β-glucan receptor Dectin-1. We have achieved efficient gene silencing in animal models, but the uptake mechanism and intracellular distribution are unclear...
July 4, 2018: Cancer Gene Therapy
Filippo Rossignoli, Giulia Grisendi, Carlotta Spano, Giulia Golinelli, Alessandra Recchia, Giulia Rovesti, Giulia Orsi, Elena Veronesi, Edwin M Horwitz, Massimo Dominici
Cellular therapies based on mesenchymal stromal/stem cells (MSC) are promising strategies in regenerative medicine and oncology. Despite encouraging results, there is still some level of concerns on inoculating MSC in cancer patients. To face this issue, one possibility resides in engineering MSC by incorporating a suicide gene in order to control their fate once infused. Strategies based on Herpes Simplex Virus Thymidine Kinase (HSV-TK) and the Cytosine Deaminase genes have been developed and more recently a novel suicide gene, namely, iCasp9, has been proposed...
June 29, 2018: Cancer Gene Therapy
Erika Durinikova, Jana Plava, Silvia Tyciakova, Pavel Skvara, Andrea Vojs Stanova, Zuzana Kozovska, Lucia Kucerova, Miroslava Matuskova
Gene-directed enzyme/prodrug therapy (GDEPT) mediated by mesenchymal stromal cells (MSC) was already approved for clinical study on a progressive disease refractory to standard therapy. In this work, we examined the effect of several GDEPT approaches on chemoresistant cells. First, we derived 5-fluorouracil (5-FU)-resistant variant of human colorectal adenocarcinoma cells HT-29 designated HT-29/EGFP/FUR. Our data show that the upregulation of thymidylate synthase (TS) and downregulation of thymidine phosphorylase (TP), orotate phosphoribosyl transferase (OPRT) and dihydropyrimidine dehydrogenase (DPD) contributed to the 5-FU resistance in cancer cells...
June 21, 2018: Cancer Gene Therapy
Dan Yue, Xiaosong Qin
It has been found that microRNAs (miRNAs) play a key role in drug resistance. The purpose of the current study was to investigate the function of miR-182 in trastuzumab resistance in breast cancer cells. The results showed that both breast cancer SKBR3 trastuzumab-resistant cells (SKBR3/TR) and BT474 trastuzumab-resistant cells (BT474/TR) were associated with miR-182 downregulation compared with their parental cells. Ectopic expression of the miR-182 mimic inhibited trastuzumab resistance, decreasing the invasion and migration of these trastuzumab-resistant cells...
June 21, 2018: Cancer Gene Therapy
Xiaochun Sun, Manhua Cui, Lingling Tong, Aichen Zhang, Kun Wang
The purpose of this work is to evaluate whether human microRNA-3129 (hsa-miR-3129) may functionally regulate cancer development, possibly through downstream target CD44 in human epithelial ovarian cancer (EOC). Direct targeting of hsa-miR-3129 on human CD44 transcript was evaluated using a dual-luciferase reporter assay. Gene expression of hsa-miR-3129 in immortal EOC cell lines was evaluated by qRT-PCR. Lentivirus-mediated hsa-miR-3129 upregulation or downregulation was conducted in SK-OV-3 and CAOV-3 cells, in which endogenous hsa-miR-3129 and CD44 expressions were then measured...
June 19, 2018: Cancer Gene Therapy
Zhiheng Cheng, Yifeng Dai, Yifan Pang, Yang Jiao, Hongmian Zhao, Zhihui Zhang, Tong Qin, Ning Hu, Yijie Zhang, Xiaoyan Ke, Yang Chen, Depei Wu, Jinlong Shi, Lin Fu
iASPP is a negative regulator of the apoptotic function of p53, and it can enhance the ability of hematopoietic stem cells to self-renew and resist chemo- and radiation therapy. Recent study showed that iASPP could impact the proliferation and apoptosis of leukemia cells by interacting with FHL2. However, whether they have prognostic significance in acute myeloid leukemia (AML) is unknown. Eighty-four AML patients with FHL2 and iASPP expression data from The Cancer Genome Atlas database were enrolled in the study...
June 18, 2018: Cancer Gene Therapy
Sun Wu, Yifeng Dai, Yuan Zhang, Xiufeng Wang, Lihua Wang, Dong Ma, Lingxiu Zhang, Yifan Pang, Yang Jiao, Mingshan Niu, Kailin Xu, Xiaoyan Ke, Jinlong Shi, Zhiheng Cheng, Lin Fu
The mutational spectrum and prognostic stratification of intermediate-risk acute myeloid leukemia (IR-AML), which accounts for a substantial number of AML, are unclear. In order to explore the prognostic significance of the mutational spectrum in IR-AML, 106 IR-AML patients were collected from The Cancer Genome Atlas database. Sixty-two patients underwent chemotherapy-only, forty-four proceeded to allogeneic hematopoietic stem cell transplantation (allo-HSCT). Fifty-five patients had more than five recurrent genetic mutations...
June 15, 2018: Cancer Gene Therapy
Song Zhao, Long Wang, Chunmei Zhang, Yu Deng, Bai Zhao, Yuxin Ren, Yingmei Fu, Xianzhi Meng
ING3 is a potential candidate tumor-suppressor gene that has been implicated in the pathogenesis of various cancers, however the exact role and mechanism of ING3 in gastric cancer (GC) remains elusive. In this study, the low expression of ING3 was validated in GC tissues and various GC cell lines. Overexpression of ING3 by transfection with pEGFP-ING3 plasmids inhibited cell proliferation in SGC-7901 and BGC-825 cells, concomitant with the decrease in the expression of PCNA, a marker for cell proliferation...
June 1, 2018: Cancer Gene Therapy
Mani Panagal, Senthil Kumar S R, Sivakurunathan P, Biruntha M, Karthigeyan M, Vincent Gopinathe, Pethanen Sivakumare, Durairaj Sekar
Myeloid leukemia (ML) is heterogeneous cancer classified by abnormal growth of myeloid cells due to genetic aberrations and mutations. It is generally categorized by clonal disorders of hematopoietic stem cells and differentiation. The molecular mechanism behind the myeloid malignancies is not yet known, but recent sequencing analysis reveals all the mutated factors. As we know that there is currently no compromise on therapy for such types of malignancies and at the present painful process like chemotherapy and radiation therapy are not effective for the treatment of ML, so there is an urgent need to develop a non-invasive biomarker for different types of ML...
May 25, 2018: Cancer Gene Therapy
Yasutaka Kojima, Naoki Otsuki, Mie Kubo, Junko Kitamoto, Eri Takata, Hiroki Saito, Kyoko Kosaka, Naoya Morishita, Natsumi Uehara, Toshiro Shirakawa, Ken-Ich Nibu
Human papillomavirus (HPV) infection has been identified as an etiologic factor of head and neck cancers (HNCs). We explored the potential use of antisense HPV RNA transcripts for gene therapy and its effect in combination with cisplatin (CDDP) for HPV-positive HNCs. We introduced the antisense RNA transcripts of the E6 and E7 genes of HPV type 16 into UM-SCC-47 cells harboring HPV 16 and YCU-T892 cells that were HPV-negative using a recombinant adenoviral vector, Ad-E6/E7-AS. We then analyzed the effects of the introduction of Ad-E7-AS on cell and tumor growth and the synergistic effect with CDDP in vitro and in vivo...
May 24, 2018: Cancer Gene Therapy
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
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
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
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
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
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
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
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
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...
May 2018: Cancer Gene Therapy
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