Ryouji Tani

Effects of insulin and transferrin on the generation of lymphokine-activated killer cells in serum-free medium

We have developed a serum-free medium designated RDSF for the generation of LAK cells based on RD6F medium, which was originally developed as a serum-free medium for the growth of myeloma and hybridoma cells. The cytotoxic activity of LAK cells generated in RDSF against Raji, K562 and oral cancer cells, is 3-4 times that of LAK cells generated in medium containing 10% human type AB serum. RDSF medium consisted of nutrient mixture supplemented with transferrin, 2-aminoethanol, 2-mercaptoethanol, sodium selenite and interleukin-2. In this study, we have found that insulin which has been shown to be the most important polypeptide hormone in serum-free media for animal cells, inhibited the generation of cytotoxic activity of LAK cells cultured from peripheral blood lymphocytes. In addition, we found that transferrin was an essential component for the growth and generation of LAK cells in serum-free culture. These results suggest that RDSF may be useful in adoptive immunotherapy for cancer as well as for studying factors involved in the growth and differentiation of LAK cells.

Photodynamic therapy using Photofrin and excimer dye laser treatment for superficial oral squamous cell carcinomas with long-term follow up.

OBJECTIVES Photodynamic therapy (PDT) is a very effective treatment for superficial malignancies that does not result in loss of normal tissue. Here, we report successful PDT treatment of superficial oral cancers and its clinical outcome with long-term follow up. MATERIALS AND METHODS Thirty-four superficial oral squamous cell carcinomas were treated with PDT, and the effects were evaluated. Each patient received Photofrin (2mg/kg) intravenously 48h prior to light irradiation. Photoradiation was performed at doses of 100-150J/cm(2) using a 630-nm wavelength excimer dye laser. RESULTS Six months after PDT, 30 patients (88.2%) showed complete responses while 9 patients (26.5%) had local relapses during long-term follow-up. The 5-year overall survival, disease-specific survival, and disease-free survival rates were 76.5%, 84.6%, and 63.3%, respectively. Lesions with red patches had a significantly higher recurrence rate than lesions with white patches. Accurate evaluation of the extent of lesions and appropriate photoradiation were important in improving outcomes. Adverse events observed included sunburn and sequestrum formation of alveolar bone. No abnormal laboratory values or systemic complications were observed. CONCLUSION PDT using Photofrin as the photosensitizer is an effective treatment modality for superficial oral carcinomas, with excellent healing and minimal side effects.

Developmental Signaling Disorders in Craniofacial Anomalies and Cancers

Normal human development requires the precise functioning and coordination of many complex pathways. Abnormalities in these signaling cascades often result in developmental perturbations, giving rise to congenital anomalies and cancers. There are 21,787 genes in each human nucleus, different gene subsets are expressed in different cell types, and different gene networks make different signal cascades. Among a large number of genes, in this review, we describe signaling disorders of sonic hedgehog and its receptor, patched-1 ; Tie2 ; fi broblast growth factor receptor in craniofacial anomalies and oral cancers.

Pathological factors involved in local failure in squamous cell carcinoma of the oral cavity: retrospective study and proposal of a new clinical classification

The control of local failure (LF) is essential to improve outcomes in patients with squamous cell carcinoma of the oral cavity (OSCC). In this study, LF of OSCC was classified into three clinical types: deep recurrence (type 1R), adjacent superficial recurrence (type 2R), and distant primary tumour (type 3R). LF was analyzed after surgical resection of OSCC to determine the validity and usefulness of this classification system. Of 257 patients with OSCC, 58 experienced LF; 21 had type 1R, 23 had type 2R, and 20 had type 3R. Clinical factors influencing LF were analyzed by log-rank test and Cox test. Type 1R was significantly related to the TN classification, resection margin status, and invasive pattern. Type 2R was strongly associated with the grade of epithelial dysplasia at the surgical margins. Type 1R rarely developed more than 1year after surgery, whereas type 2R did not develop within 2 years. Type 1R may be caused by residual cancer cells in the deep margins, and type 2R by precancerous cells remaining in the marginal epithelium and gradually becoming invasive cancer. Type 3R may be considered an independent tumour. The newly proposed clinical classification is convenient and roughly reflects the causes and mechanisms of relapse.