Ushaku Lee

Kanagawa Dental College, Йокосука, Kanagawa, Japan

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Publications (10)28.53 Total impact

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    ABSTRACT: NK4 inhibits vascularisation in tumour tissues, thereby arresting tumour growth. However, the antitumour efficacy of individual antiangiogenic molecules expressed in vivo is not sufficiently potent to induce regression in animal models. One of the strategies to overcome this disadvantage is to use chemotherapy. This study evaluated the efficacy of combining NK4 gene therapy with cisplatin to treat experimental squamous cell carcinomas. For gene therapy, biodegradable cationised gelatin microspheres were used for the controlled release of NK4 plasmid DNA. A combined regimen of antiangiogenic gene therapy and low-dose cisplatin led to a marked decrease in tumour volume and vascularity, and caused increased apoptosis compared to NK4 gene therapy alone. Moreover, combination treatment of NK4 gene therapy and low-dose cisplatin dramatically inhibited the formation of lung metastases. NK4 gene therapy combined with low-dose cisplatin may be an effective regimen for treating oral squamous cell carcinoma.
    Anticancer research 01/2011; 31(1):105-11. · 1.71 Impact Factor
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    ABSTRACT: Cancer cells metastasize by entering the lymphatic system. Regional lymph-node dissemination is the first detectable step in the metastasis of oral squamous cell carcinoma (SCC) and is highly correlated to the prognosis of the disease. Cold shock domain protein A (CSDA) is a DNA-binding protein that represses angiogenesis and lymphangiogenesis by directly binding to hypoxia response element (HRE) and serum response element (SRE). In our study we used the cell line NR-S1M, a mouse SCC model with a high rate of lymph-node metastasis. Into these cells we transfected the expression-plasmid coding for full-length mouse CSDA. Of importance, we showed that overexpression of CSDA significantly inhibits the production of VEGF-A and VEGF-C in NR-S1M cells. The overexpression of CSDA in NR-S1M cells inhibited tumor growth, inhibited regional lymph-node metastasis, and reduced the density of blood vessels and lymphatic vessels in the primary tumors in vivo. Our results support the hypothesis that VEGF-A and VEGF-C are crucial regulators of angiogenesis and lymphangiogenesis in NR-S1M cells. Therefore, they are promising targets for CSDA overexpression gene therapy to inhibit tumor growth and lymph-node metastasis in SCC.
    Clinical and Experimental Metastasis 10/2010; 27(7):539-47. · 3.46 Impact Factor
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    ABSTRACT: Inverted ductal papilloma (IDP) is a type of ductal papilloma arising in ducts of minor salivary glands. Very few cases, and no cases in Japan, have been reported. Reported herein is a case of IDP with a review of the literature. The patient was a 49-year-old man presenting with a lump in the right buccal mucosa of the premolar area of the mandible. The tumor was excised en bloc after a biopsy diagnosis of IDP. On the surface of the covering epithelium, an opening was seen to be filled with mucinous material. On cut surface the opening led to the tumor cavity. The major portion of the tumor parenchyma was made up of papillary proliferation of basaloid squamous cells. Some crypts, microcysts, and mucous cells were seen. There were no findings suggestive of a malignant tumor. The patient's postoperative course was uneventful and there has been no recurrence after 1 year's follow up. Immunohistochemical analysis of the present case supports the hypothesis that IDP originates from squamous metaplasia and proliferation of minor salivary gland duct cells.
    Pathology International 09/2006; 56(8):457-61. · 1.72 Impact Factor
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    ABSTRACT: Double-stranded RNA (dsRNA) plays a major role in RNA interference (RNAi), a process in which segments of dsRNA are initially cleaved by the Dicer into shorter segments (21-23 nt) called small interfering RNA (siRNA). These siRNA then specifically target homologous mRNA molecules causing them to be degraded by cellular ribonucleases. RNAi down regulates endogenous gene expression in mammalian cells. Vascular endothelial growth factor (VEGF) is a key molecule in vasculogenesis as well as in angiogenesis. Tumor growth is an angiogenesis-dependent process, and therapeutic strategies aimed at inhibiting angiogenesis are theoretically attractive. To investigate the feasibility of using siRNA for VEGF in the specific knockdown of VEGF mRNA, thereby inhibiting angiogenesis, we have performed experiments with a DNA vector based on a siRNA system that targets VEGF (siVEGF). It almost completely inhibited the expression of three different isoforms (VEGF120, VEGF164 and VEGF188) of VEGF mRNA and the secretion of VEGF protein in mouse squamous cell carcinoma NRS-1 cells. The siVEGF released from cationized gelatin microspheres suppressed tumor growth in vivo. A marked reduction in vascularity accompanied the inhibition of a siVEGF-transfected tumor. Fluorescent microscopic study showed that the complex of siVEGF with cationized gelatin microspheres was still present around the tumor 10 days after injection, while free siVEGF had vanished by that time. siVEGF gene therapy increased the fraction of vessels covered by pericytes and induced expression of angiopoietin-1 by pericytes. These data suggest that cationized-gelatin microspheres containing siVEGF can be used to normalize tumor vasculature and inhibit tumor growth in a NRS-1 squamous cell carcinoma xenograft model.
    Cancer Science 05/2006; 97(4):313-21. · 3.48 Impact Factor
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    ABSTRACT: A 38-year-old man with severely limited mouth opening caused by unilateral coronoid process enlargement due to osteochondroma is reported.
    Asian Journal of Oral and Maxillofacial Surgery 06/2005; 17(2):121–124.
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    ABSTRACT: NKT cells produce large amounts of cytokines associated with both the Th1 (IFN-gamma) and Th2 (IL-4) responses following stimulation of their invariant Valpha14 Ag receptor. The role of adhesion molecules in the activation of NKT cells by the Valpha14 ligand alpha-galactosylceramide (alpha-GalCer) remains unclear. To address this issue, LFA-1-/- (CD11a-/-) mice were used to investigate IL-4 and IFN-gamma production by NKT cells following alpha-GalCer stimulation. Intriguingly, LFA-1-/- mice showed increased IL-4, IL-5, and IL-13 production and polarized Th2-type responses in response to alpha-GalCer in vitro and in vivo. Furthermore, the Th2-specific transcription factor GATA-3 was up-regulated in alpha-GalCer-activated NKT cells from LFA-1-/- mice. These results provide the first genetic evidence that the adhesion receptor LFA-1 has a crucial role in Th2-polarizing functions of NKT cells.
    The Journal of Immunology 11/2004; 173(8):4976-84. · 5.52 Impact Factor
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    ABSTRACT: The possibility of inhibiting tumor growth by blocking the formation of new tumor vessels has recently received attention. Antiangiogenic tumor therapies have recently attracted intense interest because of their direct endothelial targeting and the absence of drug resistance. Local antiangiogenic gene therapy for cancer offers a potential way to achieve sustained therapeutic release of antiangiogenic substances. As a step toward this goal, we used liposomes complexed to angiostatin cDNA and targeted to human squamous cell carcinoma cell lines in vivo. Tumor cells expressing angiostatin after local gene transfer showed markedly reduced vascularity and contained many apoptotic tumor cells. These results demonstrate the potential utility of liposome-derived angiostatin for adjuvant therapy of oral cancer in humans.
    Oral Oncology 10/2002; 38(6):543-8. · 2.70 Impact Factor
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    ABSTRACT: Interleukin 12 (IL-12)-activated NK1.1+TCRalpha beta+ (NKT2) and NK1.1+TCRalpha beta- (NK) cells exhibit cytotoxic activity against a wide variety of tumor cells in the absence of prior sensitization. Here we demonstrate that the integrin adhesion receptor LFA-1 (CD11a/CD18) regulates the cytotoxic activity of IL-12-activated NKT and NK cells against YAC-1 and EL-4 tumor cells. Differentiation in vivo and the expression of the cytolytic effector molecules perforin and Fas-L were comparable in both IL-12-activated NKT and NK cells from LFA-1-/ - and LFA-1+/+ mice. However, LFA-1-/-IL-12-activated NKT and NK cells showed impaired conjugate formation with target cells. These results provide the first genetic evidence for a role for an adhesion receptor in killing by IL-12-activated NK cells.
    European Journal of Immunology 01/2001; 30(12):3723-31. · 4.97 Impact Factor
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    ABSTRACT: Interleukin 12 (IL-12)-activated NK1.1+TCRα β+ (NKT2) and NK1.1+TCRα β– (NK) cells exhibit cytotoxic activity against a wide variety of tumor cells in the absence of prior sensitization. Here we demonstrate that the integrin adhesion receptor LFA-1 (CD11a / CD18) regulates the cytotoxic activity of IL-12-activated NKT and NK cells against YAC-1 and EL-4 tumor cells. Differentiation in vivo and the expression of the cytolytic effector molecules perforin and Fas-L were comparable in both IL-12-activated NKT and NK cells from LFA-1– / – and LFA-1+ / + mice. However, LFA-1– / – IL-12-activated NKT and NK cells showed impaired conjugate formation with target cells. These results provide the first genetic evidence for a role for an adhesion receptor in killing by IL-12-activated NK cells.
    European Journal of Immunology 11/2000; 30(12):3723 - 3731. · 4.97 Impact Factor
  • European Journal of Immunology - EUR J IMMUNOL. 01/2000; 30(12):3723-3731.