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  • 1
    ISSN: 1573-7276
    Keywords: TAC-101 ; hepatocellular carcinoma ; JHH-7 ; apoptosis ; invasion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined the in vivo anti-tumor activity of the benzoic acid derivative, TAC-101 (4-[3,5- bis(trimethylsilyl)benzamido] benzoic acid), for intrahepatic spread of JHH-7 human hepatocellular carci-noma (HCC) cells and its mechanism of action. Oral administration of TAC-101 markedly inhibited liver tumor of JHH-7 cells and prolonged the life-span of tumor-bearing mice without affecting the body weight. The life-prolonging effect of TAC-101 was more effective than that of other anti-cancer agents including CDDP, 5-FU, and CPT-11 (T/C (%) of life-span ; 181 to 219, 128, 133, and 142%, respectively). In vitro, TAC-101 at the concentration of more than 10 mM showed direct cytotoxicity against JHH-7 cells caused by induction of apoptosis. Hepatocyte growth factor (HGF) enhanced the invasive ability of JHH-7 cells without affecting the cell viability. Non-cytotoxic concentrations of TAC-101 inhibited the JHH-7 invasion induced by HGF and down-regulated the expression of c-MET protein in a concentration-dependent manner. In summary, these results suggest that TAC-101 would be useful for a new class of therapeutic agents and that it may improve the prognosis of patients with liver-tumors including metastasizing tumor and HCC. ©Lippincott Williams & Wilkins
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7276
    Keywords: ATRA ; liver metastasis ; spontaneous metastasis ; survival time ; TAC-101
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined the anti-tumor effect of a novel benzoic acid derivative, TAC-101 (4-[3,5-bis(trimethylsilyl) benzamide] benzoic acid) on models with liver metastasis. Oral administration of TAC-101 significantly inhibited spontaneous liver metastasis of AZ-521 (human gastric cancer ) by orthotopic implan-tation to athymic nude mice. It also inhibited both the liver metastasis of AZ-521 induced by intrasplenic injection and the secondary lung metastasis from the liver. In addition, TAC-101 inhibited the proliferation of Co-3 (human colon adenocarcinoma) that formed a single nodule in the liver of athymic nude mice by intrahepatic implantation. The growth inhibitory effect of TAC-101 on AZ-521 experimental liver metastasis was observed when treatment was started on day 7, 14, or 21 which may correspond to the progressive stage of liver metastasis in clinical settings. Multiple administration of TAC-101 (8 mg/kg/day) significantly prolonged survival time of the animals with liver met astasis by intrasplenic injection of AZ-521 (T/C = 230%) and A549 (human lung adenocarcinoma; T/C = 186%). These effects of TAC-101 were stronger than those of 5-FU, CDDP or ATRA. Furthermore, TAC-101 inhibited the binding of AP-1 to DNA on electrophoretic mobility shift assay using nuclear extract of AZ-521 cells, although ATRA did not inhibit. These findings suggested that TAC-101 may be a candidate for a new class of anti-cancer agents for liver metastasis. © Rapid Science Ltd.
    Type of Medium: Electronic Resource
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