Showing papers by "Arimichi Takabayashi published in 2008"

Prognostic significance of the immediate early response gene X-1 (IEX-1) expression in pancreatic cancer.

Abstract: Background The immediate early response gene X-1 (IEX-1) is a stress-inducible protein that is involved in the regulation of cell proliferation and apoptosis. The aim of this study was to evaluate the prognostic significance of IEX-1 expression in pancreatic cancer.

Preventive effect of a traditional herbal medicine, Hochu-ekki-to, on immunosuppression induced by surgical stress

Abstract: To examine the effect of preoperative administering of a Japanese traditional herbal medicine, Hochu-ekki-to (TJ-41), on immunosuppression induced by surgical stress in patients with gastrointestinal malignancies. To monitor the immune functions, the mitochondrial membrane potential (MMP) and natural killer (NK) cell activity prior to and following operation were measured in peripheral blood lymphocytes (PBL) in patients with (n = 20) or without (n = 27) the preoperative administering of TJ-41 for 7 days. The plasma catecholamine and interleukin (IL)-6 levels were also analyzed prior to and following the operation. The numbers of MMP-high CD56-positive cells (NK cells) and NK cell activities in the TJ-41-treated group were significantly higher than those in the control group (P = 0.026 and P = 0.037, respectively). An elevation of plasma noradrenaline and IL-6 following surgery was also inhibited by the preoperative administering of TJ-41 (P = 0.023 and P = 0.039, respectively). A positive correlation between MMP-high CD56-positive cell numbers and NK cell activity in PBL treated with carbonyl cyanide m-chlorophenyl hydrazone (CCCP) in vitro suggested that MMP measurement in CD56-positive cells can serve as a convenient alternative to evaluate the NK cell activity. Our findings suggest that the preoperative administering of TJ-41 prevents surgical stress-induced immunosuppression by maintaining the NK cell activity and inhibiting the elevation of stress mediators.

n-Propyl gallate activates hypoxia-inducible factor 1 by modulating intracellular oxygen-sensing systems.

Abstract: HIF-1 (hypoxia-inducible factor 1) is a master regulator of cellular adaptive responses to hypoxia. The expression and transcriptional activity of the HIF-1alpha subunit is stringently controlled by intracellular oxygen tension through the action of prolyl and asparaginyl hydroxylases. In the present study we demonstrate that PG (n-propyl gallate) activates HIF-1 and expression of its downstream target genes under normoxic conditions in cultured cells and in mice. The stability and transcriptional activity of HIF-1alpha are increased by PG. PG treatment inhibits the interaction between HIF-1alpha and VHL (von Hippel-Lindau protein) and promotes the interaction between HIF-1alpha and p300, indicating that PG inhibits the activity of both prolyl and asparaginyl HIF-1alpha hydroxylases. We conclude that PG activates HIF-1 and enhances the resultant gene expression by directly affecting the intracellular oxygen sensing system in vitro and in vivo and that PG represents a lead compound for the development of a non-toxic activator of HIF-1.

Intra-arterial infusion chemotherapy with 5-fluorouracil and cisplatin in advanced pancreatic cancer: a feasibility study.

Abstract: Objective Our aim was to examine the efficacy and tolerability of intra-arterial infusion chemotherapy with 5-fluorouracil (5-FU) and cisplatin in advanced pancreatic cancer. Methods Sixteen patients with unresectable locally advanced or metastatic pancreatic cancer (12 Stage IVa and 4 Stage IVb with liver metastasis) were enrolled. The catheter for intra-arterial infusion was placed at the position to distribute chemotherapeutic drugs to both the pancreatic tumor and the liver. Continuous infusion of 5-FU (250 mg/m(2) per day, 7 days) with intermittent bolus injection of cisplatin (5 mg/m(2) per day, 5 days) was repeated twice via the catheter, followed by intermittent injection of 5-FU (375 or 750 mg/m(2)) or cisplatin (7.5 mg/m(2)) once a week. The survival of these patients was compared with that of the matched historical control patients treated with other modalities. Results In 12 Stage IVa locally advanced patients, the response rate was 58.3% (7 partial response). The median survival time was 22.0 months, and the 1-, 2-, and 3-year survival rates were 83.3%, 41.7%, and 16.7%, respectively. The locally advanced patients treated with intra-arterial infusion chemotherapy showed significantly better survival than the control patients. In contrast, Stage IVb patients with liver metastasis showed no response to the treatment (response rate, 0%). Treatment was discontinued in 2 patients until recovery from hematologic or hepatic toxicity, but fatal adverse events were not observed. Conclusion These results suggest that intra-arterial infusion chemotherapy with 5-FU and cisplatin is tolerable and feasible treatment to improve the prognosis in locally advanced pancreatic cancer patients without distant metastasis.

Uneventful splenectomy and cholecystectomy in a patient treated with anti-interleukin-6 receptor antibody therapy.

Abstract: Introduction Interleukin-6 (IL-6) is a multifunctional cytokine that regulates various aspects of the immune responses, acute phase reactions, and hematopoiesis. In rodent models, IL-6 has been suggested to be one of the essential mediators for optimal acute phase responses to infection and tissue damage. However, in humans, the roles of IL-6 in acute phase responses after surgery remain poorly understood.