Masatora Aoki

Tricin inhibits proliferation of human hepatic stellate cells in vitro by blocking tyrosine phosphorylation of PDGF receptor and its signaling pathways

4′,5,7‐Trihydroxy‐3′,5′‐dimethoxyflavone (Tricin), a naturally occurring flavone, has anti‐inflammatory potential and exhibits diverse biological activities including antigrowth activity in several human cancer cell lines and cancer chemopreventive effects in the gastrointestinal tract of mice. The present study aimed to investigate the biological actions of tricin on hepatic stellate cells (HSCs) in vitro, exploring its potential as a treatment of liver fibrosis, since HSC proliferation is closely related to the progression of hepatic fibrogenesis in chronic liver diseases leading to irreversible liver cirrhosis and hepatocellular carcinoma. Tricin inhibited platelet‐derived growth factor (PDGF)‐BB‐induced cell proliferation by blocking cell cycle progression and cell migration in the human HSC line LI90 and culture‐activated HSCs. It also reduced the phosphorylation of PDGF receptor β and the downstream signaling molecules ERK1/2 and Akt, which might be due to its tyrosine kinase inhibitor properties rather than inhibition of the direct binding between PDGF‐BB and its receptor. Our findings suggest that tricin might be beneficial in HSC‐targeting therapeutic or chemopreventive applications for hepatic fibrosis. J. Cell. Biochem. 113: 2346–2355, 2012.

Aberrant Expression of p56lck in Primary Oral Cancer

Objective: To examine whether p56lck is expressed in primary oral cancer and whether cytotoxic T-lymphocyte precursors reactive to p56lck peptides are present in the peripheral blood mononuclear cells of these patients. Materials and Methods: Oral tissue specimens were surgically obtained from 54 patients with oral squamous cell carcinoma and 20 patients with benign oral tumours. Six oral squamous cell carcinoma cell lines were used (HSC-2, HSC-3, HSC-4, OSC-20, Ca9-22, and SAS). The expression of p56lck was investigated by reverse transcriptase-polymerase chain reaction and immunohistochemical staining, and the level of interferon-gamma in the peripheral blood mononuclear cells of 10 patients with oral squamous cell carcinoma evaluated by enzyme-linked immunosorbent assay to ascertain the presence of cytotoxic T-lymphocyte precursors reactive to p56lck peptides. Results: p56lck was expressed in 38.9% (21/54) of the 54 primary oral cancer specimens obtained, but not in the benign oral tumour cells adjacent to the surrounding T cells. Only type II transcripts were expressed in the peripheral blood mononuclear cells, whereas only type I transcripts were expressed in all oral squamous cell carcinoma tissues and cell lines. Peripheral blood mononuclear cells from 7 (70%) out of 10 patients with oral cancer produced interferon-gamma in response to p56lck-derived peptides in vitro, suggesting an immune response to aberrantly expressed p56lck in these patients. Conclusion: These results may provide insight into the immunopathology of oral cancer. Further studies that demonstrate the activity of p56lck peptide-specific cytotoxic T lymphocytes may lead to the development of vaccines specific to individual oral cancer patients.