Although the systemic administration of a number of different gene products has been shown to result in the inhibition of angiogenesis and tumor growth in different animal tumor models, the relative potency of those gene products has not been studied rigorously. To address this issue, recombinant adenoviruses encoding angiostatin, endostatin, and the ligand-binding ectodomains of the vascular endothelial growth factor receptors Flk1, Flt1, and neuropilin were generated and used to systemically deliver the different gene products in several different preexisting murine tumor models. Single i.v. injections of viruses encoding soluble forms of Flk1 or Flt1 resulted in approximately 80% inhibition of preexisting tumor growth in murine models involving both murine (Lewis lung carcinoma, T241 fibrosarcoma) and human (BxPC3 pancreatic carcinoma) tumors. In contrast, adenoviruses encoding angiostatin, endostatin, or neuropilin were significantly less effective. A strong correlation was observed between the effects of the different viruses on tumor growth and the activity of the viruses in the inhibition of corneal micropocket angiogenesis. These data underscore the need for comparative analyses of different therapeutic approaches that target tumor angiogenesis and provide a rationale for the selection of specific antiangiogenic gene products as lead candidates for use in gene therapy approaches aimed at the treatment of malignant and ocular disorders.
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http://dx.doi.org/10.1073/pnas.081615298 | DOI Listing |
Cell Mol Life Sci
January 2025
Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Hypoxia, or a state of low tissue oxygenation, has been characterized as an important feature of solid tumors that is related to aggressive phenotypes. The cellular response to hypoxia is controlled by Hypoxia-inducible factors (HIFs), a family of transcription factors. HIFs promote the transcription of gene products that play a role in tumor progression including proliferation, angiogenesis, metastasis, and drug resistance.
View Article and Find Full Text PDFBioprocess Biosyst Eng
January 2025
Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea.
p-Coumaric acid (p-CA), an invaluable phytochemical, has novel bioactivities, including antiproliferative, anxiolytic, and neuroprotective effects, and is the main precursor of various flavonoids, such as caffeic acid, naringenin, and resveratrol. Herein, we report the engineering of Escherichia coli for de novo production of p-CA via the PAL-C4H pathway. As the base strain, we used the E.
View Article and Find Full Text PDFAnal Bioanal Chem
January 2025
Statistical Engineering Division, National Institute of Standards and Technology, 100 Bureau Drive, Gaithersburg, MD, 20899-8980, USA.
Closely related species of Salmonidae, including Pacific and Atlantic salmon, can be distinguished from one another based on nucleotide sequences from the cytochrome c oxidase sub-unit 1 mitochondrial gene (COI), using ensembles of fragments aligned to genetic barcodes that serve as digital proxies for the relevant species. This is accomplished by exploiting both the nucleotide sequences and their quality scores recorded in a FASTQ file obtained via Next Generation (NextGen) Sequencing of mitochondrial DNA extracted from Coho salmon caught with hook and line in the Gulf of Alaska. The alignment is done using MUSCLE (Muscle 5.
View Article and Find Full Text PDFLett Appl Microbiol
January 2025
Clinical Laboratory, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University.
MRSA's resistance poses a global health challenge. This study investigates lysine succinylation in MRSA using proteomics and bioinformatics approaches to uncover metabolic and virulence mechanisms, with the goal of identifying novel therapeutic targets. Mass spectrometry and bioinformatics analyses mapped the MRSA succinylome, identifying 8 048 succinylation sites on 1 210 proteins.
View Article and Find Full Text PDFBiotechnol Biofuels Bioprod
January 2025
Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
Background: The climate crisis and depleting fossil fuel reserves have led to a drive for 'green' alternatives to the way we manufacture chemicals, and the formation of a bioeconomy that reduces our reliance on petrochemical-based feedstocks. Advances in Synthetic biology have provided the opportunity to engineer micro-organisms to produce compounds from renewable feedstocks, which could play a role in replacing traditional, petrochemical based, manufacturing routes. However, there are few examples of bio-manufactured products achieving commercialisation.
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