PHARMACOLOGY DIVISION

5.PHARMACOLOGY DIVISION

    The research program in the Pharmacology Division focuses on the discovery of new approaches for cancer treatments that can be applied clinically. The basis of this research is a fundamental investigation of the anti-tumor mechanisms of immune effector cells and target based drugs. The more translational research projects include development of the most effective immunotherapy and appropriate schedules for different types of drugs in combination chemotherapy.
Anti-tumor Immunity of Cytotoxic T Cells, NKT Cells and Dendritic Cells

    Efficient gene transduction by an RGD-fiber modified recombinant adenovirus into dendritic cells was established.⁽⁸³⁾ Induction of tumor-specific cytotoxic T lymphocytes in prostate cancer patients using prostatic acid phosphate (PAP)-derived HLA-A2402-binding peptide was reported.⁽⁸⁴⁾ A T cell conditioned medium which efficiently induces the maturation and function of human dendritic cells was reported.⁽⁸⁵⁾ The effect of the combination of fludarabine and busulfan for chimerism after reduced-intensity stem cell transplantation was reported.⁽⁸⁶⁾ It was reported that dendritic cell maturation overrules H-2D-mediated NKT cell inhibition.⁽⁸⁷⁾
Detection of Thioredoxin (TRX) in Patients with Gastric Cancer

    Results of histochemical analysis of surgical specimens, as well as cytochemical and Northern blot analyses of gastric cancer cell lines, indicated that TRX is predominantly expressed in undifferentiated rather than differentiated type gastric cancer.^(88,⁸⁹⁾
Establishment of a Human Xenograft Derived from an Inflammatory Breast Cancer Showing Vasculogenic Mimicry

    The xenograft was reported with an absence of endothelial cells, central necrosis, and fibrosis which are associated with aggressive inflammatory breast cancer.⁽⁹⁰⁾
Biological and Biochemical Pharmacology

    The synergistic effect of platinum complex and topoisomerase I inhibitor was demonstrated.⁽⁹¹⁾ The mechanisms for the combination effects of antimitotic drugs and cytokines or radiotherapy were analyzed.^(92-⁹⁴⁾ The drug-drug interactions were observed in topoisomerase inhibitor and 5-FU.⁽⁹⁵⁾ Antitumor activities of target-based drugs were evaluated in vitro and in vivo.⁽⁹⁶⁾ To demonstrate proof of the principle and to establish useful surrogate markers for tumor response,⁽⁹⁷⁾ molecular correlative studies were conducted for target-based drugs such as gnidimacrin, ⁽⁹⁸⁾ YTA0040, and E7070.⁽⁹⁴⁾ Cell cycle regulatory molecules such as cdk2 and cyclins were found to be determinants of the actions of these drugs. Increased expression levels of oncoprotein 18,⁽⁹⁹⁾ osteopontin,⁽¹⁰⁰⁾ and angiogenesis related genes⁽¹⁰¹⁾ in lung tumors correlated with cellular sensitivity to chemotherapy and target-based therapy in lung cancer.
Drug Resistance

    A human ATP-binding cassette transporter SMRP and its mouse homologue were isolated previously, and the SMRP transcript was found to be a splicing variant of the MRP5 gene. Increased expression of the MRP5 gene was associated with sensitivity to adriamycin and its resistance in lung cancer cells.⁽⁹⁸⁾ A benzothiazepine analogue reversed cisplatin-resistance in human lung cancer cells in vitro and in vivo by increasing intracellular accumulation of the drugs.⁽¹⁰²⁾




5.PHARMACOLOGY DIVISION



	The research program in the Pharmacology Division focuses on the discovery of new approaches for cancer treatments that can be applied clinically. The basis of this research is a fundamental investigation of the anti-tumor mechanisms of immune effector cells and target based drugs. The more translational research projects include development of the most effective immunotherapy and appropriate schedules for different types of drugs in combination chemotherapy. Anti-tumor Immunity of Cytotoxic T Cells, NKT Cells and Dendritic Cells Efficient gene transduction by an RGD-fiber modified recombinant adenovirus into dendritic cells was established.⁽⁸³⁾ Induction of tumor-specific cytotoxic T lymphocytes in prostate cancer patients using prostatic acid phosphate (PAP)-derived HLA-A2402-binding peptide was reported.⁽⁸⁴⁾ A T cell conditioned medium which efficiently induces the maturation and function of human dendritic cells was reported.⁽⁸⁵⁾ The effect of the combination of fludarabine and busulfan for chimerism after reduced-intensity stem cell transplantation was reported.⁽⁸⁶⁾ It was reported that dendritic cell maturation overrules H-2D-mediated NKT cell inhibition.⁽⁸⁷⁾ Detection of Thioredoxin (TRX) in Patients with Gastric Cancer Results of histochemical analysis of surgical specimens, as well as cytochemical and Northern blot analyses of gastric cancer cell lines, indicated that TRX is predominantly expressed in undifferentiated rather than differentiated type gastric cancer.^(88,⁸⁹⁾ Establishment of a Human Xenograft Derived from an Inflammatory Breast Cancer Showing Vasculogenic Mimicry The xenograft was reported with an absence of endothelial cells, central necrosis, and fibrosis which are associated with aggressive inflammatory breast cancer.⁽⁹⁰⁾ Biological and Biochemical Pharmacology The synergistic effect of platinum complex and topoisomerase I inhibitor was demonstrated.⁽⁹¹⁾ The mechanisms for the combination effects of antimitotic drugs and cytokines or radiotherapy were analyzed.^(92-⁹⁴⁾ The drug-drug interactions were observed in topoisomerase inhibitor and 5-FU.⁽⁹⁵⁾ Antitumor activities of target-based drugs were evaluated in vitro and in vivo.⁽⁹⁶⁾ To demonstrate proof of the principle and to establish useful surrogate markers for tumor response,⁽⁹⁷⁾ molecular correlative studies were conducted for target-based drugs such as gnidimacrin, ⁽⁹⁸⁾ YTA0040, and E7070.⁽⁹⁴⁾ Cell cycle regulatory molecules such as cdk2 and cyclins were found to be determinants of the actions of these drugs. Increased expression levels of oncoprotein 18,⁽⁹⁹⁾ osteopontin,⁽¹⁰⁰⁾ and angiogenesis related genes⁽¹⁰¹⁾ in lung tumors correlated with cellular sensitivity to chemotherapy and target-based therapy in lung cancer. Drug Resistance A human ATP-binding cassette transporter SMRP and its mouse homologue were isolated previously, and the SMRP transcript was found to be a splicing variant of the MRP5 gene. Increased expression of the MRP5 gene was associated with sensitivity to adriamycin and its resistance in lung cancer cells.⁽⁹⁸⁾ A benzothiazepine analogue reversed cisplatin-resistance in human lung cancer cells in vitro and in vivo by increasing intracellular accumulation of the drugs.⁽¹⁰²⁾