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Cancer Gene Therapy

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
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
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
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
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
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
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
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
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
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
Haoyu Zhou, Zhihua Sun, Songwei Li, Xiaofeng Wang, Xuejun Zhou
Long non-coding RNAs (lncRNAs) have been demonstrated to be critical regulators in tumorigenesis. LncRNA SPRY4-IT1 has been identified as critical regulator for hepatocellular carcinoma and ovarian cancer. However, the potential role and clinical value of SPRY4-IT1 in human thyroid cancer (TC) still remain unclear and need to be uncovered. Our current study was aimed to ascertain the biological role of expression of SPRY4-IT1 in TC tissues and cells. Our findings revealed that the level of SPRY4-IT1 was significantly upregulated in TC tissues and cell lines, which was correlated with poor prognosis...
December 12, 2017: Cancer Gene Therapy
Meng Liu, Zheng Han, Qing-Xi Zhu, Jie Tan, Wei-Jie Liu, Yan-Fen Wang, Wei Chen, Yan-Li Zou, Yi-Shan Cai, Xia Tian, Xiaodong Huang
Gastric cancer is the fourth most common type of cancer. Liver-intestine cadherin (CDH17) has been found to be involved in the proliferation and apoptosis of gastric cancer cells. Cisplatin is one of the most widely used antineoplastic agents in the treatment of solid tumor and hematological malignancies. However, the mechanism of enhancing cisplatin-inducing effects on human gastric cancer BGC823 cells by blocking CDH17 gene, both in vitro and in vivo, remains to be clarified. In this study, we investigated the signaling pathway by which cisplatin induces apoptosis by blocking CDH17 gene in gastric cancer BGC823 cells...
December 4, 2017: Cancer Gene Therapy
X Gong, M Huang
Glioma has been identified as one of the most aggressive primary tumors. Long non-coding RNAs (lncRNAs), with length larger than 200 bp, have drawn increasing attention to their abnormal expression and regulation function in carcinogenesis. However, the role of lncRNAs in glioma remains largely unknown. Maternally expressed gene 3 (MEG3), also known as gene-trap locus 2 (GTL2), is an imprinted gene, and is encoded by the MEG3 transcript of the DLK1/MEG3 locus on human chromosome, or Meg3 on mouse chromosome...
September 2017: Cancer Gene Therapy
Y Furukawa, A Takasu, Y Yura
Herpes simplex virus type 1 (HSV-1) is one of the most widely studied viruses for oncolytic virotherapy. In squamous cell carcinoma (SCC) cells, the role of autophagy induced by neurovirulence gene-deficient HSV-1s in programmed cell death has not yet been elucidated. The oncolytic HSV-1 strain RH2, which lacks the γ34.5 gene and induces the fusion of human SCC cells, was used. RH2 replicated and induced cell death in SCC cells. RH2 infection was accompanied by the aggregation of microtubule-associated protein 1 light chain 3 (LC3) in the cytoplasm, the conversion of LC3-I to LC3-II and the formation of double-membrane vacuoles containing cell contents...
September 2017: Cancer Gene Therapy
J H Rothman, O Surriga, E de Stanchina, S D Vasudeva, G K Schwartz
Peptide nucleic acid (PNA) oligomers are DNA mimics, which are capable of binding gene sequences 1000-fold more avidly than complementary native DNA by strand invasion and effectively obstruct transcription. Irreversibly obstructing the transcription or replication of a gene sequence, such as BRAF(V600E), offers a potential route to specifically target the cancer cell itself. We have employed PNA oligomers to target BRAF(V600E) in a sequence-specific complementary manner. These PNAs have been modified by appending configurationally stabilizing cationic peptides in order to improve their cellular delivery and target avidity...
September 2017: Cancer Gene Therapy
Q-Y Shang, C-S Wu, H-R Gao
The present study explored the effect that deoxycytidine kinase (DCK) knockdown had on proliferation, apoptosis and tumorigenicity in vivo of cervical cancer HeLa cells. Human cervical cancer HeLa cells that had received no prior treatment were selected from the HeLa group. The HeLa-negative control (NC) group consisted of cells that had undergone an empty vector treatment, and finally the HeLa-short hairpin RNA (shRNA) group included cells that were treated by means of shRNA-DCK expression. DCK expressions were evaluated by quantitative real-time polymerase chain reaction in addition to western blotting assays...
September 2017: Cancer Gene Therapy
J-I Lai, Y-C Lai, Y-C Chen, N-K Wang, J-N Pan, W-S Wang, S-C Chang
Lung cancer is one of the leading causes of death from cancer worldwide, with a poor prognosis in advanced cases. In the past decade, epidermal growth factor receptor (EGFR) inhibitors have shown significant efficacy towards treatment for EGFR mutant lung cancer. Expanding our knowledge of oncogenic EGFR signaling pathways is therefore of highly importance for the cancer field. Recently it has been proposed that mutant EGFR transcriptionally silences the TET1 (ten-eleven translocation methylcytosine dioxygenase 1) gene in cellular and animal models of lung cancer...
September 2017: Cancer Gene Therapy
Y Jie, W He, X Yang, W Chen
Sijunzi decoction (SJZD) is a traditional Chinese medicine prescription for the prevention and treatment of colorectal cancer. Our study is aimed to identify the potential therapeutic target of SJZD. Microarray analysis was performed on the patients with colorectal cancer under treatment of SJZD. The mRNA targets of SJZD were predicted by BATMAN-TCM database and were further identified by integrated analysis of expression data from TCGA. The correlation of gene expression and clinical characteristics was analyzed...
September 2017: Cancer Gene Therapy
Y Lu, T Qin, J Li, L Wang, Q Zhang, Z Jiang, J Mao
MicroRNAs (miRNAs) have been proven to be involved in cell metastasis and angiogenesis by interaction with the target mRNAs. Evidence has been confirmed that miR-140-5p is a tumor suppressor in human cancers such as breast cancer. However, the potential molecular mechanism of miR-140-5p in breast cancer invasion and angiogenesis is still poorly understood. According to our study, we reported that miR-140-5p inhibited the tumor invasion and angiogenesis of breast cancer cells both in vitro and in vivo by targeting VEGF-A...
September 2017: Cancer Gene Therapy
Y Zhou, B Sheng, Q Xia, X Guan, Y Zhang
In recent years, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been shown to play important roles in tumor biological function. The aim of this study was to investigate the diagnostic and prognostic value of lncRNA H19 and miR-21 expression in non-small-cell lung cancer (NSCLC). H19 and miR-21 expression was measured in tumor tissues and corresponding non-tumor lung tissues from 200 patients by quantitative reverse transcription polymerase chain reaction. Moreover, the in vitro and in vivo effects of H19 knock out in A549 cells were investigated...
August 2017: Cancer Gene Therapy
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