AI Article Synopsis
- The study focused on designing a hybrid version of TNF-alpha for systemic anti-tumor therapy by examining how its molecular size affects its effectiveness.
- It was found that as the PEG modification of TNF-alpha increased, its in vitro bioactivity decreased, especially with higher PEG molecular weights.
- The most effective hybrid TNF-alpha formulations had a size between 100 and 110 kDa, showing more than ten times the anti-tumor efficacy compared to the unmodified TNF-alpha, highlighting the importance of molecular size in determining activity.
Article Abstract
To design hybrid tumour necrosis factor-alpha (TNF-alpha) applicable to systemic anti-tumour therapeutic use, we assessed the relationships among the molecular size of hybrid TNF-alpha, in vitro bioactivity and in vivo anti-tumour potency. Natural human TNF-alpha was covalently modified with polyethylene glycol (PEG) of various number-average molecular weights (Mn = 2000, 5000, 12,000). The in vitro bioactivity of PEG-modified TNF-alpha s decreased with an increase in the degree of PEG modification, irrespective of the molecular weight of PEG. This decrease in the specific bioactivity markedly increased with an increase in the molecular weight of the attached PEG. The in vivo anti-tumour effects of the hybrid TNF-alpha s with a molecular size from 100 to 110 kDa, which had more than 50% of specific bioactivity of native TNF-alpha, were significantly superior to other PEG-TNF-alpha s. These hybrid TNF-alpha s showed over ten times greater anti-tumour effects than native TNF-alpha. Thus, the molecular size, which was determined by the degree of PEG modification and PEG molecular weight, influences the specific activity and anti-tumour effects of hybrid TNF-alpha.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2077111 | PMC |
| http://dx.doi.org/10.1038/bjc.1996.495 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
L. protects cerebral ischemia/reperfusion injury via arachidonic acid/p53-mediated apoptosis axis.
Front Pharmacol
December 2024
State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Introduction: Stroke is a debilitating disease and the second leading cause of death worldwide, of which ischemic stroke is the dominant type. L., also known as safflower, has been used to treat cerebrovascular diseases, especially ischemic stroke in many Asian countries.
View Article and Find Full Text PDFProphylactic direct oral anticoagulants vs. low molecular weight heparin after urological surgery: A systematic review and meta-analysis.
Arab J Urol
September 2024
Department of Surgery, Sabah Al-Ahmad Urology Center, Kuwait City, Kuwait.
Purpose: To compare the outcomes of using prophylactic direct oral anti-coagulants (DOAC) and low-molecular-weight heparin (LMWH) after major urologic surgery.
Materials And Methods: Systematic literature searches of MEDLINE, Embase, Web of Science, and Cochrane CENTRAL were performed up to 9 November 2023, and protocols were registered on PROSPERO (CRD42024494424). The primary outcomes were post-operative incidence of VTE and bleeding.
The Patterns of P53, E-Cadherin, β-Catenin, CXCR4 and Podoplanin Expression in Oral Squamous Cell Carcinoma Suggests a Hybrid Invasion Model: an Immunohistochemical Study on Tissue Microarrays.
Head Neck Pathol
January 2025
Department of Oral Pathology, School of Dentistry, University of São Paulo, São Paulo, Brazil.
Purpose: Oral squamous cell carcinoma (OSCC) is a significant public health challenge associated with high mortality rates primarily due to its invasive and metastatic behavior. This study aimed to evaluate the expression patterns of five critical biomarkers: β-catenin, E-cadherin, podoplanin (PDPN), CXCR4, and p53 in OSCC tissues and to investigate their correlations with clinicopathologic features and patient outcomes.
Methods: We conducted an immunohistochemical analysis utilizing tissue microarrays (TMAs) from 95 patients diagnosed with primary OSCC.
Interactive effects of salinity, redox, and colloids on greenhouse gas production and carbon mobility in coastal wetland soils.
PLoS One
December 2024
Environmental Molecular Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, United States of America.
Coastal wetlands, including freshwater systems near large lakes, rapidly bury carbon, but less is known about how they transport carbon either to marine and lake environments or to the atmosphere as greenhouse gases (GHGs) such as carbon dioxide and methane. This study examines how GHG production and organic matter (OM) mobility in coastal wetland soils vary with the availability of oxygen and other terminal electron acceptors. We also evaluated how OM and redox-sensitive species varied across different size fractions: particulates (0.
View Article and Find Full Text PDFDenovo variants in POGZ and YY1 genes: The novel mega players for neurodevelopmental syndromes in two unrelated consanguineous families.
PLoS One
January 2025
Department of Psychiatry, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, United States of America.
Novel denovo variants of exome sequences are major cause of pathogenic neurodevelopmental disorders with a dominant genetic mechanism that emphasize their heterogeneity and complex phenotypes. White Sutton syndrome and Gabriele-de-Vries syndrome are congenital neuro-impairments with overlap of severe intellectual disability, microcephaly, convulsions, seizures, delayed development, dysmorphism of faces, retinal diseases, movement disorders and autistic traits. POGZ gene codes for pogo transposable element-derived zinc-finger protein and YY1 gene regulates transcription, chromatin, and RNA-binding proteins that have been associated with White Sutton and Gabriele-de-Vries syndromes, in recent data.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!