HOX and PBX gene dysregulation as a therapeutic target in glioblastoma multiforme

Background: Glioblastoma multiforme (GBM) is the most common high-grade malignant brain tumour in adults and arises from the glial cells in the brain. The prognosis of treated GBM remains very poor with 5-year survival rates of 5%, a figure which has not improved over the last few decades. Currently, there is a modest 14-month overall median survival in patients undergoing maximum safe resection plus adjuvant chemoradiotherapy. HOX gene dysregulation is now a widely recognised feature of many malignancies. Methods: In this study we have focused on HOX gene dysregulation in GBM as a potential therapeutic target in a disease with high unmet need. Results: We show significant dysregulation of these developmentally crucial genes and specifically that HOX genes A9, A10, C4 and D9 are strong candidates for biomarkers and treatment targets for GBM and GBM cancer stem cells. We evaluated a next generation therapeutic peptide, HTL-001, capable of targeting HOX gene over-expression in GBM by disrupting the interaction between HOX proteins and their co-factor, PBX. HTL-001 induced both caspase-dependent and -independent apoptosis in GBM cell lines. Conclusion: In vivo biodistribution studies confirmed that the peptide was able to cross the blood brain barrier. Systemic delivery of HTL-001 resulted in improved control of subcutaneous murine and human xenograft tumours and improved survival in a murine orthotopic model

A T-cell engager-armed oncolytic vaccinia virus to target the tumor stroma

Aim: Cancer-associated fibroblasts (CAFs) are the key cellular components of the tumor stroma. CAFs express fibroblast activation protein (FAP) and FAP-targeted immunotherapies have shown potent antitumor effects in preclinical mouse studies, highlighting their central role in tumorigenesis. However, safety concerns have been raised in regard to FAP-targeted immunotherapies since bone marrow failure and cachexia were observed in transgenic models and preclinical studies. Here, we describe a novel oncolytic virotherapy by locally targeting FAP within tumor tissue. Methods: T-cell engager-armed oncolytic vaccinia virus (TEA-VV) that encodes a secretory bi-specific T-cell engager consisting of two single-chain variable fragments specific for murine CD3 and fibroblast activation protein (mFAP-TEA-VV) was generated. The antitumor effects of mFAP-TEA-VV were compared to unmodified VVs using standard in vitro immunological assays and an immunocompetent B16 melanoma mouse model. Results: In vitro, the ability of mFAP-TEA-VV to replicate within tumor cells and induce oncolysis was similar to that of unmodified VVs. However, in co-culture assays, only mFAP-TEA-VV induced bystander killing of noninfected FAP-expressing cells in the presence of murine T-cells. In vivo, mFAP-TEA-VV enhanced viral titer within the tumor and had potent antitumor activity in comparison to control VVs in an immunocompetent B16 melanoma mouse model. Importantly, the improved viral spread of mFAP-TEA-VV correlated with the destruction of tumor stroma. Conclusion: Arming oncolytic VVs with an FAP-targeted T-cell engager may be a promising improvement to oncolytic virus therapy for solid tumors

Discussion on High-yield Cultivation and Assembling and Supporting Technology of Selenium-enriched Rice and Rapeseed Rotation in Taoyuan County

Taoyuan County is a large grain and rapeseed production county. Taking advantage of the resource advantage of soil rich in selenium in Taoyuan County, it promotes high-yield cultivation and assembly technology of selenium-rich rice and rapeseed rotation in one-season rice area, optimizing the aggregate structure of the soil, improving the soil ecology and reducing the content of heavy metals in the soil, laying the foundation for the continuous increase in agricultural efficiency and farmers’ income. Through rice and rapeseed rotation, the overwintering base of rice field borers are reduced, and the incidence of pests and diseases in the coming year is effectively reduced. The popularization of assembling and supporting technologies for rice-rapeseed rotation cropping and the promotion of high-quality varieties and planting techniques can increase the farmers' income significantly. This paper will describe the methods and technologies in detail from three aspects: the assembling and supporting methods of selenium-enriched rice and rapeseed rotation high-yield cultivation, main points of the supporting technology for the rice selenium-enriched cultivation and main points of supporting technology for the rapeseed selenium-enriched cultivation

Replication and Spread of Oncolytic Herpes Simplex Virus in Solid Tumors

Oncolytic herpes simplex virus (oHSV) is a highly promising treatment for solid tumors. Intense research and development efforts have led to first-in-class approval for an oHSV for melanoma, but barriers to this promising therapy still exist that limit efficacy. The process of infection, replication and transmission of oHSV in solid tumors is key to obtaining a good lytic destruction of infected cancer cells to kill tumor cells and release tumor antigens that can prime anti-tumor efficacy. Intracellular tumor cell signaling and tumor stromal cells present multiple barriers that resist oHSV activity. Here, we provide a review focused on oncolytic HSV and the essential viral genes that allow for virus replication and spread in order to gain insight into how manipulation of these pathways can be exploited to potentiate oHSV infection and replication among tumor cells

The complete chloroplast genome sequence of Exochorda racemosa (Lindl.) Rehd.

Exochorda racemosa (Lindl.) Rehd. is a traditional medicinal herb widely distributed in China. Here, we reported the complete chloroplast genome sequence of E. racemosa. The chloroplast genome (160,398 bp) was composed of four regions, with a large single-copy (LSC, 88,458 bp) region, a small single-copy (SSC, 19,190 bp) region, and two inverted repeat (IR, 26,375 bp) regions. The overall GC content was 36.48%. A total of 131 genes were predicted with 86 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The phylogenetic analysis showed that E. racemosa had a close relationship with E. serratifolia

Detection of Mercury Ion with High Sensitivity and Selectivity Using a DNA/Graphene Oxide Hybrid Immobilized on Glass Slides

Excessive mercury ions (Hg2+) cause great pollution to soil/water and pose a major threat to human health. The high sensitivity and high selectivity in the Hg2+ detection demonstrated herein are significant for the research areas of analytical chemistry, chemical biology, physical chemistry, drug discovery, and clinical diagnosis. In this study, a series of simple, low-cost, and highly sensitive biochips based on a graphene oxide (GO)/DNA hybrid was developed. Hg2+ is detected with high sensitivity and selectivity by GO/DNA hybrid biochips immobilized on glass slides. The performance of the biosensors can be improved by introducing more phosphorothioate sites and complementary bases. The best limit of detection of the biochips is 0.38 nM with selectivity of over 10:1. This sensor was also used for Hg2+ detection in Dendrobium. The results show this biochip is promising for Hg2+ detection

Sequencing and phylogenetic analysis of the complete chloroplast genome of Arisaema heterophyllum Blume

Arisaema heterophyllum Blume is a perennial medicinal herb widely distributed in China, Korea and Japan. In this study, the complete chloroplast genome sequence of A. heterophyllum was assembled and characterized based on high-throughput sequencing data. The whole chloroplast genome is 170,610 bp in length and contains 95,485 bp large single-copy (LSC) and 22,605 bp small single-copy (SSC) regions separated by a pair of 26,260 bp inverted repeat (IR) regions. It contained a total of 129 genes, including 84 protein-coding genes, 37 tRNA genes, and 8 rRNA genes, with an overall GC content of 34.5%. A phylogenetic tree reconstructed by 30 chloroplast genomes reveals that A. heterophyllum is mostly related to the same genus A. ringens, A. franchetianum and A. erubescens. The complete chloroplast genome of A. heterophyllum was the firstly reported and deposited at GenBank under accession number MZ424448