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T Tokunaga

Publications and source records attributed to T Tokunaga.

At least 37 records · Page 2Linked to original sources
PubMed2001

Gene expression of angiogenesis related factors in glioma.

Angiogenesis plays an important role in growth and proliferation of cancer. Various angiogenic and angiostatic factors regulate angiogenesis. In this study, we examined gene expression of the angiopoietin family including angiopoietin 1 (Ang1) and angiopoietin 2 (Ang2) in 39 gliomas and 5 glioma-xenografts by RT-PCR. Ang1 and Ang2 genes were expressed in 54%, and 77% of gliomas, respectively. The expression of Ang1 was significantly correlated with the expression of Ang2. Both Ang1 and Ang2 were shown to be expressed in the glioma cells. Ang2 gene expression was correlated with VEGF gene expression. Angiopoietin molecules may synergistically cooperate in growth and vascularization in glioma.

Angiopoietin-1↗
PubMed2001

Interleukin 10 expression is correlated with thrombospondin expression and decreased vascular involvement in colon cancer.

Interleukin 10 (IL-10) is an immuno-suppressive cytokine produced by T-lymphocytes, and a regulatory molecule for angiogenesis in various cancers. We examined IL-10 gene expression in 53 colon cancer patients who underwent surgical resection. IL-10 gene expression was correlated with TSP1 and TSP2 gene expression (P=0.0049, P=0.0285). Colon cancer with IL-10 gene expression (19/53) showed significantly decreased venous involvement (P=0.0433). The mean vessel counts in the colon cancers with IL-10 gene expression were significantly lower than those without IL-10 gene expression (P<0.001). These results suggested that IL-10 stimulates angiostatic factor gene expression, and results in suppression of venous involvement.

Adenocarcinoma↗
PubMed2001

Significant correlation between interleukin 10 expression and vascularization through angiopoietin/TIE2 networks in non-small cell lung cancer.

The expression of interleukin 10 (IL-10) is correlated with clinical prognosis in non-small cell lung cancer [NSCLC (H. Hatanaka et al., ANN: ONCOL:, 11: 815--819, 2000)]. However, the effects of IL-10 expression on vascularization in NSCLC are not apparent. We examined the gene expression of IL-10/IL-10 receptor and various angiogenic/angioinhibitory factors in 95 NSCLC samples to determine the correlation between IL-10 production and vascularization. Vascular endothelial growth factor, angiopoietin [Ang (Ang-1 and Ang-2)], thrombospondin, brain-specific angiogenesis inhibitor 1, vascular endothelial growth factor receptors (KDR and flt-1), and Ang receptor (TIE2) gene expression were evaluated by reverse transcription-PCR. The cellular localization of these factors and vascularity in the cancer stroma were examined immunohistochemically. Seventy-eight (82.1%) and 93 (97.9%) of these 95 NSCLCs were positive for IL-10 and IL-10 receptor, respectively. Ang-1, Ang-2, and TIE2 gene expression was seen in 76 (97.4%), 73 (93.6%), and 78 (100%) of 78 IL-10-positive NSCLCs, respectively, and was significantly correlated with IL-10 gene expression (P < 0.0088, <0.0008, and 0.0305, respectively; Fisher's exact method). The localizations of Ang-1, Ang-2, and TIE2 were confirmed within tumor cells immunohistochemically. Vascular number and measurement area were significantly higher in the IL-10-positive NSCLCs (33.500 +/- 9.299/microm(2) and 4.742 +/- 1.287%) as compared with IL-10-negative NSCLCs (10.611 +/- 2.839/microm(2) and 0.718 +/- 0.331%; Mann-Whitney U test, P = 0.0039). The IL-10 expression did not show any significant correlation with the expression of other factors. These results suggested that tumor-produced IL-10 promotes stromal vascularization through expression of Ang-1, Ang-2, and TIE2.

Angiogenesis Inhibitors↗
PubMed2000

Modified guanidines as potential chiral superbases. 2. Preparation Of 1,3-unsubstituted and 1-substituted 2-iminoimidazolidine derivatives and a related guanidine by the 2-chloro-1, 3-dimethylimidazolinium chloride-induced cyclization of thioureas

Simple preparation methods for modified guanidines were explored for new chiral superbases. Thus, (4S,5S)-4,5-diphenyl- and diastereomeric cyclohexane-fused 2-iminoimidazolidines were prepared from (1S,2S)-1,2-diphenylethylenediamine and (1R,2R)- or (1S,2S)-1, 2-diaminocyclohexanes through cyclization of protected thiourea intermediates with 2-chloro-1,3-dimethylimidazolinium chloride (DMC) as a key reaction. In the (4S,5S)-4,5-diphenyl series 1-methyl-2-iminoimidazolidines and 2-diethylaminoimidazoline were also prepared as related guanidines.

Journal Article↗
PubMed2000

Modified guanidines as potential chiral superbases. 3. Preparation Of 1,4,6-triazabicyclooctene systems and 1,4-disubstituted 2-iminoimidazolidines by the 2-chloro-1,3-dimethylimidazolinium chloride-induced cyclization of guanidines with a hydroxyethyl substituent

Simple preparation methods of modified guanidines have been explored as potential chiral superbases. Thus, 3,7,8-trisubstituted and 3,6,7, 8-tetrasubstituted 1,4,6-triazabicyclooctene systems were prepared from (1S,2S)-1,2-diphenylethylenediamine through stepwise 2-chloro-1, 3-dimethylimidazolinium chloride (DMC)-induced cyclizations of protected thioureas to the corresponding 2-iminoimidazolidines and then of 2-(2-hydroxyethylimino)imidazolidines to the bicyclic systems. Linear guanidines with a 2-hydroxyethyl functional group were prepared by the reaction of carbodiimides with 2-amino alcohols. Reaction of linear-type guanidines with DMC followed by base treatment afforded 1,4-disubstitued 2-iminoimidazolidines. Furthermore, another type of 1,4,6-triazabicyclooctene was also prepared through double DMC-induced cyclization of guanidines with two 2-hydroxyethyl substituents.

Journal Article↗
PubMed2000

Effects of pterygium on corneal spherical power and astigmatism.

OBJECTIVE: To evaluate prospectively the corneal refractive status before and after pterygium surgery and its relationship with preoperative pterygium size. DESIGN: Prospective, nonrandomized, comparative (self-controlled) trial. PARTICIPANTS: One hundred thirty-six eyes undergoing primary pterygium removal surgery. MAIN OUTCOME MEASURES: Corneal spherical power, astigmatism, surface regularity index (SRI), and surface asymmetry index (SAI) before and after surgery, and the preoperative pterygium size. RESULTS: Before surgery, pterygium size significantly correlated with spherical power (Pearson's correlation coefficient, r = -0.370, P < 0.001), astigmatism (r = 0.600, P < 0.001), SRI (r = 0.367, P < 0.001), and SAI (r = 0.387, P < 0.001). The surgery significantly increased spherical power of the cornea, whereas astigmatism, SRI, and SAI were significantly decreased by the surgery (P < 0.01, paired t test with Bonferroni's correction of P value for multiple comparison). Surgically induced changes in spherical power (r = 0.598, P < 0.001) and astigmatism (r = 0.653, P < 0.001) significantly correlated with the preoperative pterygium size. Precise prediction of the magnitude of refractive changes based on the preoperative pterygium size was difficult. CONCLUSIONS: The presence of pterygium and its removal significantly influence the corneal refraction including spherical power, astigmatism, asymmetry, and irregularity, with the larger pterygium exerting the greater influence.

Adult↗
PubMed2000

Influence of excimer laser photorefractive keratectomy on the posterior corneal surface.

PURPOSE: To investigate the influence of excimer laser photorefractive keratectomy on the refraction and geometry of the posterior corneal surface. SETTING: Miyata Eye Hospital, Miyazaki, Japan. METHODS: Thirty-seven eyes of 21 patients with refractive errors of -2.00 to -9.75 diopters (D) were treated with the VISX Twenty-Twenty excimer laser system. The refractive and anteroposterior changes in the posterior corneal surface were measured using scanning-slit corneal topography (Orbscan, Orbtek, Inc.) preoperatively and 1 week and 1 and 3 months postoperatively. RESULTS: Mean posterior corneal refraction was -6.51 D +/- 0. 29 (SD) preoperatively; it decreased to -7.00 +/- 0.49 D, -7.00 +/- 0.55 D, and -6.92 +/- 0.42 D at 1 week, 1 month, and 3 months, respectively (P <.001, Tukey multiple comparison). Mean forward shift of the posterior corneal surface was 29.5 +/- 1.9 microm, 34.4 +/- 3.4 microm, and 54.3 +/- 4.0 microm at 1 week, 1 month, and 3 months, respectively. The amount of posterior corneal refractive change correlated with the degree of forward shift (r= -0.691, P <. 001). The residual corneal thickness correlated with the refractive change (r = 0.524, P <.001) and the forward shift (r = -0.851, P <. 001) of the posterior corneal surface. CONCLUSION: Photorefractive keratectomy induced significant refractive changes in the posterior corneal surface and forward shift of the cornea, both of which correlated with the thinness of the residual cornea.

Adult↗
PubMed2000

Ribozyme approach to downregulate vascular endothelial growth factor (VEGF) 189 expression in non-small cell lung cancer (NSCLC).

The aim of this study was to further clarify the role of the cell-associated isoform of vascular endothelial growth factor (VEGF189) on tumour growth and vascularity. Five isoforms of VEGF have been identified with different biological activities. VEGF121, VEGF145, VEGF165, VEGF189, VEGF206 are generated by alternative splicing. We used a hammerhead-type ribozyme (V189Rz) to suppress VEGF189 mRNA. The V189Rz specifically cleaved exon 6 of VEGF189 mRNA, but showed no activity against the VEGF121 or VEGF165 isoforms. The V189Rz was introduced into the human non-small cell lung cancer (NSCLC) cell line (OZ-6/VR). The expression level of VEGF189 mRNA was decreased in the OZ-6/VR cells, while VEGF121 and 165 expression was unaltered. The OZ-6/VR cells xenotransplanted into nude mice showed markedly reduced vascularisation and growth, whereas the cell line did not show any decreased growth under tissue culture conditions. The OZ-6/VR cells (1 x 10(5) cells/mouse) formed no tumours, whereas the parental OZ-6 cells formed large tumours within 8 weeks. The specific suppression of VEGF189 by the ribozyme decreased vascularity and xenotransplantability of the lung cancer cell line. Thus, the cell-associated isoform of VEGF, VEGF189, might have a key role in stromal vascularisation and the growth of NSCLC xenografts in vivo.

Animals↗
PubMed2000

Absolute stereochemistry of gastric antisecretory compound P371A1 and its congener P371A2 from streptomyces species P371.

Absolute configurations of the gastric antisecretory compound P371A1 (1) and its congener P371A2 (2) from Streptomyces sp. P371 were determined on the basis of identification of the methyl glycosides 9, 10, and 11 obtained by the acid degradation of 1 and 2, as well as application of the modified Mosher method to the P371A2 C-glycoside MTPA esters 7 and 8 and observation of the excitation chiralities in the P371A2 C-glycoside benzoate derivatives 5 and 6.

Aminoglycosides↗
PubMed2000

Clinical implications of interleukin (IL)-10 induced by non-small-cell lung cancer.

BACKGROUND: The type 2 cytokine interleukin (IL)-10 has been reported to inhibit the antitumour activity of the regional immunity against various neoplasms. Certain lung cancers produce IL-10, but the clinical significance of IL-10 expression is not well understood. PATIENTS AND METHODS: We examined IL-10 and IL-10 receptor (IL-10R) mRNA expression in 82 non-small-cell lung cancers (NSCLC) by reverse transcription-polymerase chain reaction (RT-PCR) assay. Immunohistochemistry (IHC) and enzyme immunoassay (EIA) were applied to evaluate the cellular localisation and the serum levels of IL-10. RESULTS: RT-PCR assay revealed IL-10 mRNA expression in 68 (83%) of 82 NSCLC surgical specimens (40 of 50 adenocarcinomas, 22 of 26 squamous cell carcinomas, 5 of 5 large-cell carcinomas, 1 of 1 adenosquamous-cell carcinoma). RT-PCR assay also revealed IL-10R mRNA expression in 79 cases of NSCLC (96.1%). IL-10 expression was confirmed within tumour cells by IHC. EIA showed no significant serum IL-10 elevation in the 12 NSCLC positive for IL-10 mRNA expression (0-2.99 pg/ml). The NSCLC patients with IL-10 production showed significantly poorer prognosis than those without IL-10 production (P < 0.05, Kaplan Meier, log-rank test). CONCLUSIONS: These results suggested that the cytoplasmic IL-10 correlated to clinical prognosis, and that IL-10 expression is a prognostic factor for NSCLC.

Carcinoma, Non-Small-Cell Lung↗
PubMed2000

Adenovirus-mediated anti-K-ras ribozyme induces apoptosis and growth suppression of human pancreatic carcinoma.

Human pancreatic cancer is a lethal malignancy, and the lesions show a very high incidence of point mutations of the K-ras oncogene. These alterations can be used as potential targets for specific ribozyme (Rz)-mediated growth suppression of the cancer cells. We designed an anti-K-ras Rz against mutant K-ras gene transcripts (codon 12, GGT to GTT) and generated a recombinant adenovirus (rAd) to express the Rz (rAd/anti-K-ras Rz). More than 95% of Capan-1 human pancreatic cells were infected with rAd/anti-K-ras Rz when treated with the virus at 200 plaque-forming units/cell. The virus, rAd/anti-K-ras Rz, significantly suppressed mutant K-ras gene expression and inhibited the growth of Capan-1 cells. At 3 days postinfection, we observed maximum growth suppression of the cells, characteristic morphological changes of apoptosis such as nuclear condensation and oligonucleosomal DNA fragmentation, and suppression of bcl-2 oncoprotein. These changes were not found in control virus-infected cells. Our results indicated that the virus rAd/anti-K-ras Rz specifically down-regulated the K-ras/bcl-2 pathway and induced apoptotic changes in Capan-1 pancreatic carcinoma cells. High-efficiency adenovirus-mediated delivery of anti-K-ras Rz could become a significant gene therapy strategy against human pancreatic cancer.

Adenoviridae↗
PubMed2000

Ribozyme-mediated inactivation of mutant K-ras oncogene in a colon cancer cell line.

Mutation of c-K-ras oncogene is an important step in progression of colon cancer. We used a hammerhead ribozyme (KrasRz) against mutated K-ras gene transcripts (codon 12, GTT) to inactivate mutant K-ras function in the colon cancer cell line SW480, harbouring a mutant K-ras gene. The beta-actin promoter-driven KrasRz sequence (pHbeta/KrasRz) was introduced into these cells (SW480/KrasRz), and we evaluated its effects on growth of the colon cancer. The gene expression of angiogenesis-related molecules (vascular endothelial growth factor and thrombospondin) was also estimated in SW480/KrasRz. KrasRz specifically and efficiently cleaved the mutant K-ras mRNA but not wild-type mRNA in vitro. SW480/KrasRz showed decreased growth rate under tissue culture conditions (P< 0.01, Dunnett's test). The xenotransplantability of SW480/KrasRz (XeSW480/KrasRz) was significantly decreased in nude mice (P< 0.05, Fisher's exact test). Tumour volume of the xenografts XeSW480/KrasRz was significantly smaller than that of XeSW480/DisKrasRz (P< 0.01, Dunnett's test). Gene expression of VEGF was suppressed in SW480/KrasRz, while TSP1 gene expression was enhanced. The SW480/KrasRz cells showed apoptosis-related features including nuclear condensation and DNA fragmentation. These results suggested that the hammerhead ribozyme-mediated inactivation of the mutated K-ras mRNA induced growth suppression, apoptosis and alteration of angiogenic factor expression.

Animals↗
PubMed2000

The cecum and dietary short-chain fructooligosaccharides are involved in preventing postgastrectomy anemia in rats.

Dietary short-chain fructooligosaccharides (Sc-FOS) stimulate absorption of calcium and magnesium in the large intestine of rats. In this study, we examined whether Sc-FOS stimulate iron absorption in the large intestine by monitoring recovery from anemia in gastrectomized rats, with or without cecectomy. The rats were divided into four groups, i.e., sham-operated (Sham), gastrectomized only (GX), cecectomized only (CX) and both gastrectomized and cecectomized (GCX). Half of the rats in each group were fed a control diet (AIN-93G) and the other half were fed a Sc-FOS-containing diet (75 g/kg diet) for 28 d. Hematocrit (Ht) and hemoglobin concentration (Hb) were measured at the start, and on d 14 and 28 after the start of feeding. On the final day of the study, total blood was collected. Gastrectomy significantly decreased Ht and Hb, but cecectomy did not influence these variables. Dietary Sc-FOS prevented the decrease in Ht and Hb significantly. In the gastrectomized rats, the effectiveness of Sc-FOS in preventing postgastrectomy anemia was significantly diminished by cecectomy. These results suggest that the effect of Sc-FOS in increasing absorption of iron in gastrectomized rats takes place in part in the cecum. The cecum plays an important role in the mechanism by which Sc-FOS prevent postgastrectomy anemia.

Analysis of Variance↗
PubMed2000

Neuropilin-2 expression affects the increased vascularization and is a prognostic factor in osteosarcoma.

Osteosarcoma is a malignant bone tumor characterized by hypervascularity. Neuropilins (NRPs), which is expressed by human tumor cells, is known to be a potent receptor for vascular endothelial growth factor (VEGF). We examined NRPs mRNA expression in 30 osteosarcomas. The osteosarcomas with NRP2 expression (n=24) showed a significantly increased vascularity (P<0.0014, Mann-Whitney U test). Osteosarcomas with NRP2 showed significantly poorer prognosis than those without NRP2 (P=0.016, Wilcoxon's test). These results suggest that NRP acts as a VEGF-amplifier in a paracrine or autocrine manner in the osteosarcoma. NRP2 expression cooperatively promotes angiogenesis and growth in osteosarcomas with VEGF expression.

Bone Neoplasms↗