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Ken Takeda

Publications and source records attributed to Ken Takeda.

45 records · Page 3Linked to original sources
PubMed2002

Intraoperative radiation therapy (IORT) for previously untreated malignant gliomas.

BACKGROUND: Intraoperative radiation therapy (IORT) is one of the methods used to deliver a large single dose to the tumor tissue while reducing the exposure of normal surrounding tissue. However, the usefulness of intraoperative electron therapy for malignant gliomas has not been established. METHODS: During the period from 1987 to 1997, 32 patients with malignant gliomas were treated with IORT. The histological diagnoses were anaplastic astrocytoma in 11 patients and glioblastoma in 21 patients. Therapy consisted of surgical resection and intraoperative electron therapy using a dose of 12--15 Gy (median, 15 Gy). The patients later underwent postoperative external radiation therapy (EXRT) with a median total dose of 60 Gy. Each of the 32 patients treated with IORT was randomly matched with patients who had been treated with postoperative EXRT alone (control). Patients were matched according to histological grade, age, extent of tumor removal, and tumor location. RESULTS: In the anaplastic astrocytoma group, the one-, two- and five-year survival rates were 81%, 51% and 15%, respectively in the IORT patients and 54%, 43% and 21%, respectively in the control patients. In the glioblastoma group, one-, two- and five-year survival rates were 63%, 26% and 0%, respectively in the IORT patients and 70%, 18% and 6%, respectively in the control patients. There was no significant difference between survival rates in the IORT patients and control patients in either the anaplastic astrocytoma group or glioblastoma group. CONCLUSIONS: IORT dose not improve survival of patients with malignant gliomas compared to that of patients who have received EXRT alone.

Adult↗
PubMed2002

GM-CSF induces expression of gp91phox and stimulates retinoic acid-induced p47phox expression in human myeloblastic leukemia cells.

All-trans retinoic acid (ATRA) combined with granulocyte macrophage colony-stimulating factor (GM-CSF) synergistically increases superoxide-generating activity in human myeloblastic leukemia ML-1 cells. ATRA is known to increase the expression of some NADPH components; however, little is known about the effect of GM-CSF on the expression of these components. We examined the expression of NADPH oxidase components in ML-1 cells treated with ATRA, GM-CSF, or a combination of ATRA and GM-CSF. Expression of p47phox and gp91phox proteins increased markedly after treatment with both reagents. p47phox expression was increased by ATRA alone, and the expression was increased synergistically by the combination of ATRA with GM-CSF. gp91phox was increased by ATRA or GM-CSF alone. The expression of p47phox and gp91phox mRNA underwent similar changes to those seen in protein level. These results indicate that GM-CSF induces expression of gp91phox and enhances ATRA-induced p47phox expression. We speculate that the remarkable induction of gp91phox and p47phox protein is associated with an increase in superoxide-generating activity due to the synergistic effect of ATRA plus GM-CSF.

Base Sequence↗
PubMed2002

Red wine polyphenols increase calcium in bovine aortic endothelial cells: a basis to elucidate signalling pathways leading to nitric oxide production.

1. The present study investigates the mechanisms by which polyphenolic compounds from red wine elicit Ca(2+) mobilization in bovine aortic endothelial cells (BAECs). Two polyphenol-containing red wine extracts, red wine polyphenolic compounds (RWPC) and Provinols, and delphinidin, an anthocyanin were used. 2. RWPC stimulated a Ca(2+)-dependent release of nitric oxide (NO) from BAECs accounting for the relaxation of endothelium-denuded rat aortic rings as shown by cascade bioassay. 3. RWPC, Provinols and delphinidin increased cytosolic free calcium ([Ca(2+)](i)), by releasing Ca(2+) from intracellular stores and by increasing Ca(2+) entry. 4. The RWPC-induced increase in [Ca(2+)](i) was decreased by exposure to ryanodine (30 microM), whereas Provinols and delphinidin-induced increases in [Ca(2+)](i) were decreased by bradykinin (0.1 microM) and thapsigargin (1 microM) pre-treatment. 5. RWPC, Provinols and delphinidin-induced increases in [Ca(2+)](i) were sensitive to inhibitors of phospholipase C (neomycin, 3 mM; U73122, 3 microM) and tyrosine kinase (herbimycin A, 1 microM). 6. RWPC, Provinols and delphinidin induced herbimycin A (1 microM)-sensitive tyrosine phosphorylation of several intracellular proteins. 7. Provinols released Ca(2+) via both a cholera (CTX) and pertussis toxins (PTX)-sensitive pathway, whereas delphinidin released Ca(2+) only via a PTX-sensitive mechanism. 8. Our data contribute in defining the mechanisms of endothelial NO production caused by wine polyphenols including the increase in [Ca(2+)](i) and the activation of tyrosine kinases. Furthermore, RWPC, Provinols and delphinidin display differences in the process leading to [Ca(2+)](i) increases in endothelial cells illustrating multiple cellular targets of natural dietary polyphenolic compounds.

Animals↗
PubMed2002

Radiation therapy for limited-stage small-cell esophageal cancer.

Between 1985 and 1999, 20 patients with limited-stage small-cell carcinoma of the esophagus (SCEC) received radiation therapy at Tohoku University Hospital and Miyagi Cancer Center Hospital. Twelve patients received definitive radiation therapy and eight patients received postoperative prophylactic irradiation after surgery. The 1-, 2-, and 5-year survival rates of all cases were 44%, 37%, and 19%, respectively. Distant metastasis was the most frequent pattern of recurrence. Survival rates differed significantly between the 6 patients who were not treated with chemotherapy (median survival time, 5 months) and the 14 patients who were (24 months) (p = 0.0061). Good local control rates can be obtained by definite or postoperative radiation therapy for SCEC. However, SCEC should be regarded as a systemic disease, and chemotherapy should be given. Multiinstitutional studies are needed to obtain sufficiently large populations for investigation and optimization of local therapy for this disease.

Aged↗
PubMed2002

Differential expression of genes during TPA-induced differentiation of human prostatic cancer TSU-Pr1 cells.

We are interested in the possibility of a new prostate cancer therapy that would control tumor malignancy via induction of terminal cell differentiation. We previously reported that 12-O-tetra-decanoylphorbol-13-acetate (TPA) induces differentiation into cells with characteristics of microglia and decreases the malignant characteristics of human prostatic cancer TSU-Pr1 cells. To investigate the mechanism underlying differentiation of TSU-Pr1 cells, we attempted to identify genes expressed during differentiation using differential display. We identified four genes expressed differentially after TPA treatment. Levels of expression of two genes, human flavoprotein subunit of complex II and JKTBP, were downregulated by TPA, and expression of two genes, human golgin p245 and bcl-xL, was upregulated. Moreover, we found that the changes in expression of flavo-protein, JKTBP and bcl-xL induced by TPA were blocked by treatment with protein kinase C (PKC) or mitogen-activated protein (MAP) kinase inhibitors that prevent TPA-induced differentiation of TSU-Pr1 cells. These results suggest that the differential expression of these genes is associated with TPA-induced differentiation of TSU-Pr1 cells. We expect that understanding the roles of these genes during differentiation will provide for new approaches and therapeutic targets for treatment of prostate cancer.

Antineoplastic Agents↗
PubMedDate not supplied

Up-regulation of p21(WAF1/CIP1) levels leads to growth suppression of prostate cancer cell lines.

In a previous study, we found that TPA-mediated up-regulation of p21(WAF1/CIP1) induces growth arrest and differentiation of the human prostate cancer cell line TSU-Pr1. We investigated the effect of 12-O-tetra-decanoylphorbol-13-acetate (TPA) on growth and p21(WAF1/CIP1) protein levels in four prostate cancer cell lines. TPA treatment suppressed proliferation of the androgen-insensitive prostate cancer cell lines DU145 and PC-3. DU145 and PC-3 cells, however, showed neither morphological changes nor differentiation after TPA treatment. In contrast, TPA induced apoptosis of the androgen-sensitive prostate cancer cell line LNCaP. TPA induced up-regulation of p21(WAF1/CIP1) protein levels in all four cancer cell lines and this up-regulation was regulated by PKC in all four, but MAP kinase was associated with regulation only in TSU-Pr1 cells. Moreover, transient transfection with Adv-p21 resulted in growth arrest of all four cell lines. These data suggest that increased p21(WAF1/CIP1) production directly suppresses proliferation of prostate cancer cells regardless of androgen sensitivity. The pathway of TPA-induced increases in p21(WAF1/CIP1) levels was regulated by PKC. We thus conclude that p21(WAF1/CIP1) is a good candidate for use in treatment of prostate cancers because it suppresses proliferation of several prostate cancer cell lines.

Cell Differentiation↗
PubMedDate not supplied

Significance of plasminogen-activation system in the formation of macroscopic types and invasion in esophageal carcinoma.

BACKGROUND: The roles of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in the formation of macroscopic types and invasion were investigated. MATERIALS AND METHODS: A total of 40 surgically-resected esophageal carcinoma tissues were immunohistochemically stained, and the expression of uPA, PAI-1 and the uPA/PAI-1 ratio, were evaluated. RESULTS: The expression of uPA was significantly stronger in the macroscopically infiltrative type (n = 20: p = 0.0027), whereas PAI-1 was significantly stronger in the localized type (n = 20: p = 0.0005). The uPA/PAI-1 ratio was significantly higher in the infiltrative type (p < 0.0001). A significant correlation was found between the U/P ratio and the depth of tumor invasion (r = 0.511, p = 0.0014). Analysis of tumors of uniform size (4.0-6.0 cm in length), showed that the depth of invasion was significantly greater in the infiltrative type (p = 0.0038). CONCLUSION: The results demonstrated that uPA and PAI-1 play important roles in invasion and formation of macroscopic types of esophageal carcinoma.

Aged↗
PubMedDate not supplied

Bone morphogenetic protein-2 suppresses invasiveness of TSU-Pr1 cells with the inhibition of MMP-9 secretion.

Bone morphogenetic protein (BMP), which is a member of the transforming growth factor beta (TGF-beta) superfamily, has powerful osteoinductive effects and various biological activities in a variety of cells. The effect of BMP-2 on the human carcinoma cell line TSU-Pr1 was examined. BMP-2 was found to inhibit the migration and invasiveness, but not the proliferation, of TSU-Pr1 cells. Gel zymography for matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA) detection revealed that BMP-2 down-regulated the activity of MMP-9, but not of MMP-2 or uPA. BMP-2 also reduced the secretion of MMP-9 into the culture media, but did not affect the secretion of MMP-2, Timp-1, Timp-2 or Timp-3. These results suggest that BMP-2 inhibits migration and decreases MMP-9 secretion to suppress the invasiveness of TSU-Pr1 cells. This is the first report of a role for BMP signaling in reducing the invasiveness of cancer cells.

Bone Morphogenetic Protein 2↗