Tetsuharu Kaneko

Liver X receptor reduces proliferation of human oral cancer cells by promoting cholesterol efflux via up-regulation of ABCA1 expression

Liver X receptors (LXRs) contribute not only to maintain cholesterol homeostasis but also to control cell growth. However, the molecular mechanisms behind the LXR-mediated anti-proliferative effects are largely unknown. Here we show, by immunohistochemistry, that LXRα and LXRβ are differentially distributed in oral stratified squamous epithelia. By immunohistochemical and Western blot analyses, we also reveal that LXRα is abundantly expressed in human oral squamous cell carcinoma (HOSCC) tissues and cell lines. Cell counting, BrdU labeling and cell cycle assay indicated that LXR stimulation led to significant reduction of proliferation in HOSCC cells. Importantly, our study highlights, by using RNA interference, that the ATP-binding cassette transporter A1 (ABCA1)-accelerated cholesterol efflux is critical for the growth inhibitory action of LXRs in HOSCC cells. Moreover, we demonstrate that LXR activation reduces the growth of xenograft tumour of HOSCC cells in mice accompanied by the upregulation of ABCA1 expression and the decline of cholesterol levels in the tumour. These findings strongly suggested that targeting the LXR-regulated cholesterol transport, yielding in lowering intracellular cholesterol levels, could be a promising therapeutic option for certain types of cancers.

A case of nonleukemic granulocytic sarcoma in the gingiva, uterus, and breast

Granulocytic sarcoma (GS) is defined as a localized tumor mass composed of immature cells of granulocytic cells in extramedullary sites. We report a case of nonleukemic GS in the gingiva, uterus, and breast. A 47-year-old woman was referred to the Department of Gynecology in our hospital because of irregular genital bleeding. At the same time, she presented at our department and the Department of Breast Surgery because of oral mucositis and a breast lump. An ulcerative lesion was observed in the right maxillary gingiva, and GS was diagnosed on biopsy. Bone marrow examination revealed the absence of leukemia. Because the same diagnosis was made in the uterus and right breast, chemotherapy was performed according to the acute myelogenous leukemia protocol in the Department of Hematology. Although she achieved complete remission, the GS recurred in the left breast after 1 year 4 months. Therefore, allogeneic hematopoietic stem cell transplantation was performed after administering the same chemotherapy regimen as that used for primary treatment. However, GS recurred in the bone marrow 90 days after transplantation, and the patient died 2 years 9 months after starting primary treatment.