Basic studies on chemoprevention for head and neck cancer

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It is well known that all-trans retinoic acid (ATRA) differentiate acute promyelocytic leukemia (APL) cells and ATRA is an efficacious drug for APL.The usefullness of retinoids in chemoprevention for premalignant lesions in the head and neck has been reported. The outcome of cases with advanced head and neck carcinomas is poor in spite of curative treatments, i.e., radiation therapy and/or surgery with chemotherapy and/or immunotherapy. Therefore, a new treatment modality is indispensable for advanced head and neck carcinimas.The inhibitive effects of cell differetiation-related agents, vesnarinone, pamidronate disodium, ATRA and derivatives of Vitamin D3, i.e., 22-oxacalcitriol (OCT) and 1alpha, 25(OH)2D3, on DNA synthesis of human head and neck squamous cell carcinoma cell lines were examined. Futhermore, the sensitivity against chemotherapeutic drugs and morphologocal changes of treated tumor cells was compared to that of non-treated ones. After the treatment with each drug, the cel … More l growth of treated tumor cells was inhibited dependetly on the concentration of each treatment drug. In the derivatives of Vitamin D3, OCT showd a stronger suppression on DNA synthesis than 1alpha, 25(OH)2D3 did. In terms of the comparison of suppressive effects on cell growth between the treatment with OCT and/or ATRA,the combined treatment represented the strongest suppression of DNA synthesis. In cell cycle examination, the treatment resulted in a increase of cells in G0-G1, with an accompanying decrease of cells in S phase. With regard to sensitivity tests using of CDDP or 5-FU,IC50 for CDDP decreased markedly after the treatment with ATRA or vesnarinone. The treated tumor cells showed a less responsiveness to epidermal growth factor. In addition, morphological changes were observed by microscopic analysis after OCT and/or ATRA treatment. The treated cells became bigger and extended the dendrites.These findings suggest the potential usefulness of cell differentiation-related drugs in treatment modality for human squamous cell carcinomas of the head and neck. Less