Abstract：
:Genetically modified vaccinia viruses (VACVs) have been shown to possess profound oncolytic capabilities. However, tumor cell resistance to VACVs may endanger broad clinical success. Using cell mass assays, viral replication studies, and fluorescence microscopy, we investigated primary resistance phenomena of cell lines of the NCI-60 tumor cell panel to GLV-1h94, a derivative of the Lister strain of VACV, which encodes the enzyme super cytosine deaminase (SCD) that converts the prodrug 5-fluorocytosine (5-FC) into the chemotherapeutic compound 5-fluorouracil (5-FU). After treatment with GLV-1h94 alone, only half of the cell lines were defined as highly susceptible to GLV-1h94-induced oncolysis. When adding 5-FC, 85% of the cell lines became highly susceptible to combinatorial treatment; none of the tested tumor cell lines exhibited a "high-grade resistance" pattern. Detailed investigation of the SCD prodrug system suggested that the cytotoxic effect of converted 5-FU is directed either against the cells or against the virus particles, depending on the balance between cell line-specific susceptibility to GLV-1h94-induced oncolysis and 5-FU sensitivity. The data provided by this work underline that cellular resistance against VACV-based virotherapy can be overcome by virus-encoded prodrug systems. Phase I/II clinical trials are recommended to further elucidate the enormous potential of this combination therapy.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Berchtold S,Beil J,Raff C,Smirnow I,Schell M,D'Alvise J,Gross S,Lauer UMdoi
10.3390/ijms21207618subject
Has Abstractpub_date
2020-10-15 00:00:00issue
20issn
1422-0067pii
ijms21207618journal_volume
21pub_type
杂志文章abstract：:This study describes the simple synthesis of new (quinazolin-4-ylamino) methylphosphonates via microwave irradiation. Substituted-2-aminobenzonitrile reacted with 1,1-dimethoxy-N,N-dimethylmethanamine at a reflux condition to obtain N'-(substituted-2-cyanophenyl)-N,N-dimethylformamidine (1). The subsequent reaction of...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
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abstract：:It is widely recognized that many chronic infections of the human body have a polymicrobial etiology. These include diabetic foot ulcer infections, lung infections in cystic fibrosis patients, periodontitis, otitis, urinary tract infections and even a proportion of systemic infections. The treatment of mixed infection...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2021-01-06 00:00:00
abstract：:Neurodegenerative disorders affect around one billion people worldwide. They can arise from a combination of genomic, epigenomic, metabolic, and environmental factors. Aging is the leading risk factor for most chronic illnesses of old age, including Alzheimer's and Parkinson's diseases. A progressive neurodegenerative...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2019-02-08 00:00:00
abstract：:O-mannosylation is implicated in protein quality control in Saccharomyces cerevisiae due to the attachment of mannose to serine and threonine residues of un- or misfolded proteins in the endoplasmic reticulum (ER). This process also designated as unfolded protein O-mannosylation (UPOM) that ends futile folding cycles ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
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更新日期：2019-12-10 00:00:00
abstract：:In addition to its role in ribosome biogenesis, ribosomal protein S3 (RPS3), a component of the 40S ribosomal subunit, has been suggested to possess several extraribosomal functions, including an apoptotic function. In this study, we demonstrated that in the mouse brain, the protein levels of RPS3 were altered by the ...
journal_title：International journal of molecular sciences
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更新日期：2018-09-12 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2017-06-20 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2016-05-23 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2018-02-08 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2019-03-05 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2019-04-15 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms19103203
更新日期：2018-10-17 00:00:00
abstract：:Interferon (IFN)-γ is mainly secreted by CD4+ T helper 1 (Th1), natural killer (NK) and NKT cells after skin injury. Although IFN-γ is well known regarding its inhibitory effects on collagen synthesis by fibroblasts in vitro, information is limited regarding its role in wound healing in vivo. In the present study, we ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20225657
更新日期：2019-11-12 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms18112380
更新日期：2017-11-09 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms20215341
更新日期：2019-10-27 00:00:00
abstract：:The current interest of the scientific community for research in the field of calcium sensing in general and on the calcium-sensing Receptor (CaR) in particular is demonstrated by the still increasing number of papers published on this topic. The extracellular calcium-sensing receptor is the best-known G-protein-coupl...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms19040999
更新日期：2018-03-27 00:00:00
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journal_title：International journal of molecular sciences
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doi：10.3390/ijms21165787
更新日期：2020-08-12 00:00:00
abstract：:Distal-less homeobox 5 (Dlx5) is a negative regulator of adipogenesis. Dlx5 expression is decreased by adipogenic stimuli, but the mechanisms of Dlx5 downregulation by adipogenic stimuli have not yet been determined. Here, we tested the impact of cAMP/PKA (protein kinase A) signaling induced by 3-isobutyl-1 methyl xan...
journal_title：International journal of molecular sciences
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doi：10.3390/ijms19103161
更新日期：2018-10-14 00:00:00
abstract：:Accurate and sensitive determination of hematopoietic chimerism is a crucial diagnostic measure after allogeneic stem cell transplantation to monitor engraftment and potentially residual disease. Short tandem repeat (STR) amplification, the current "gold standard" for chimerism assessment facilitates reliable accuracy...
journal_title：International journal of molecular sciences
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doi：10.3390/ijms17091515
更新日期：2016-09-09 00:00:00
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
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更新日期：2020-08-06 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19051318
更新日期：2018-04-28 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
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更新日期：2018-03-31 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2021-01-13 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms19113691
更新日期：2018-11-21 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
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更新日期：2015-12-31 00:00:00
abstract：:Colorectal cancer is one of the most common malignancies and is the second-leading cause of cancer-related death world-wide, which is linked to genetic mutations, epigenetic alterations, and oncogenic signaling activation. MicroRNAs, one of the categories of epigenetics, have been demonstrated significant roles in car...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms18040890
更新日期：2017-04-22 00:00:00
abstract：:NAC (NAM, ATAF1/2, and CUC2) transcription factors play important roles in many biological processes, and mainly bind to the NACRS with core sequences "CACG" or "CATGTG" to regulate gene expression. However, whether NAC proteins can bind to other motifs without these core sequences remains unknown. In this study, we e...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
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更新日期：2018-10-21 00:00:00
abstract：:In this review, the effect of pharmaceuticals (PHRs) and personal care products (PCPs) on microalgal growth and metabolism is reported. Concentrations of various PHRs and PCPs that cause inhibition and toxicity to growths of different microalgal strains are summarized and compared. The effect of PHRs and PCPs on micro...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms20102492
更新日期：2019-05-20 00:00:00
