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Thymidine phosphorylase expression is associated with both increase of intratumoral microvessels and decrease of
T Matsuura1, I Kuratate, K Teramachi
1First Department of Pathology, Tottori University, Faculty of Medicine, Yonago, Japan.
Cancer Research
|October 16, 1999
Summary
Thymidine phosphorylase (dThdPase) promotes colorectal cancer growth by increasing blood vessels and reducing apoptosis, independent of p53. This suggests dThdPase as a potential therapeutic target for unfavorable prognoses.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Thymidine phosphorylase (dThdPase), also known as platelet-derived endothelial cell growth factor, is upregulated in various human carcinomas.
- Elevated dThdPase expression correlates with increased intratumoral microvessel density (IMVD) and poorer patient prognosis.
- The precise role of dThdPase in colorectal carcinoma progression, particularly concerning apoptosis and angiogenesis, requires further elucidation.
Purpose of the Study:
- To investigate the role of dThdPase in apoptosis, cell proliferation, IMVD, and p53 expression in human colorectal carcinomas.
- To determine the association between dThdPase expression levels and clinicopathological features, including Dukes' stage.
- To explore the potential mechanisms by which dThdPase influences tumor growth and patient outcomes.
Main Methods:
- Human colorectal carcinoma tissues were analyzed for dThdPase expression.
- Tumor samples were categorized based on dThdPase expression (Category I: positive; Category II: negative).
- Intratumoral microvessel density (IMVD) and apoptotic indices (AIs) were quantified and compared between categories.
- p53 expression frequency was assessed in relation to dThdPase levels.
Main Results:
- Significantly higher IMVD was observed in dThdPase-positive tumors (Category I) compared to dThdPase-negative tumors (Category II) across all stages (P < 0.01).
- Mean apoptotic indices (AIs) were significantly lower in Category I tumors than in Category II tumors, irrespective of Dukes' stage (P < 0.01).
- A significant inverse correlation was found between AI and IMVD (P < 0.001).
- No significant difference in p53 expression frequency was detected between the two categories.
Conclusions:
- dThdPase expression promotes human colonic carcinoma growth by enhancing intratumoral microvessel formation and suppressing apoptosis.
- The observed attenuation of apoptosis appears to be mediated through a p53 gene-independent pathway.
- These findings highlight dThdPase as a key factor in colorectal cancer progression and suggest its potential as a therapeutic target.