Novel HER2 selective tyrosine kinase inhibitor, TAK-165, inhibits bladder, kidney and androgen-independent prostate cancer in vitro and in vivo
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概要
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Purpose: TAK-165 is a new potent inhibitor of human epidermal growth factor receptor 2 (HER2) tyrosine kinase. Several reports suggest HER2 expression in bladder cancer, renal cell carcinoma (RCC) and androgen-independent prostate cancer. We therefore investigated the antitumor effect of TAK-165 on these urological cancer cells. Materials and methods: Western blot analysis was performed to confirm HER2 expression in cell lines. To study in vitro efficacy, cells were treated with TAK-165 at various concentrations for 72 h and then counted using a hemocytometer. Then the IC50 value was calculated. In the xenograft model, after the tumor reached 200-300 mm3 in volume, mice were orally administered TAK-165 10 mg/kg per day or 20 mg/kg per day or saline for 14 consecutive days (n = 6-8). Results: HER2 expression was observed in HT1376, UMUC3, T24 (bladder), ACHN (kidney), DU145, LNCaP, LN-REC4 (prostate), although the expression level in these cells was weak compared with BT474 (a breast cancer cell line which expresses HER2 strongly). IC50 was varied from 0.09 to greater than 25 μmol/L in the bladder cancer cell line. ACHN cells were less sensitive in vitro. The prostate cancer cell lines studied were all sensitive (IC50 0.053-4.62 μmol/L). In the xenograft model, treatment with TAK-165 significantly inhibited growth of UMUC-3, ACHN, and LN-REC4. The antitumor effect (T/C [%] = growth of TAK-165 treated tumor/average growth of control tumor × 100) after 14 days treatment were 22.9%, 26.0%, and 26.5% in UMUC3, ACHN and LN-REC4, respectively. Conclusions: TAK-165 may be a hopeful new agent for bladder, kidney and androgen-independent prostate cancer.
- Blackwell Publishingの論文
- 2006-05-01
著者
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NAMIKI Mikio
Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical
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Kohno K
Department Of Molecular Biology School Of Medicine University Of Occupational And Environmental Heal
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Kohno Kimitoshi
九州大学 医学系研究院 医化学
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Kohno Kimitoshi
Department Of Molecular Biology University Of Occupational And Environmental Health School Of Medici
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Koshiba Ken
Departments Of Urology And Pathology Kitasato University School Of Medicine
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KOSHIDA Kiyoshi
Department of Urology, School of Medicine, Kanazawa University
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Koshida Kiyoshi
Department Of Urology Kanazawa University Hospital
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MIZOKAMI Atsushi
Department of Urology
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NAGASAWA JOJI
Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medicin
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YOSHIDA SEI
Pharmaceutical Research Division, Takeda Chemical Industries
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NAITO KENICHIRO
Pharmaceutical Research Division, Takeda Chemical Industries
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Mizokami Atsushi
Department Of Integrative Cancer Therapy And Urology Kanazawa University Graduate School Of Medical
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Mizokami Atsushi
Department Of Urology Kanazawa University Graduate School Of Medical Science
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Namiki Mikio
Department Of Applied Physics And Science And Engineering Research Laboratory Waseda University
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Yoshida Sei
Pharmaceutical Research Division Takeda Chemical Industries
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Nagasawa Joji
Department Of Integrative Cancer Therapy And Urology Kanazawa University Graduate School Of Medicine
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Namiki Mikio
Department Of Integrated Cancer Therapy And Urology Andrology Unit Kanazawa University Graduate Scho
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Koshida Kiyoshi
Department Of Urology Graduate School Of Medicine Kanazawa University
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Mizokami Atsushi
Department Of Urology Kanazawa University Hospital
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Koshida Kiyoshi
Department Of Urology Kanazawa University School Of Medicine
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Namiki Mikio
Department Of Integrative Cancer Therapy And Urology Kanazawa University Graduate School Of Medical
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Kondo Katsuyoshi
Department Of Urology Okayama Red Cross General Hospital
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Namiki Mikio
Department Of Integrative Cancer Therapy And Urology Kanazawa University Graduate School Of Medical
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Namiki Mikio
Department Of Urology Kanazawa University Graduate School Of Medical Science
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Mizokami Atsushi
Department Of Integrative Cancer Therapy And Urology Kanazawa University Graduate School Of Medical
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Naito Kenichiro
Pharmaceutical Research Division Takeda Chemical Industries
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Namiki Mikio
Department Of Applied Physics : Science And Engineering Research Laboratory Waseda University
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Mizokami Atsushi
Department Of Integrative Cancer Therapy And Urology Kanazawa University Graduate School Of Medical
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Koshida Kiyoshi
Department Of Molecular Biology School Of Medicine University Of Occupational And Environmental Health
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Koshiba Ken
Department Of Molecular Biology University Of Occupational And Environmental Health
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Naito Kenjiro
Pharmaceutical Research Division, Takeda Chemical Industries
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Mizokami Atsuhi
Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science
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