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Biomedical subjects

Naoki Tsuji

Publications and source records attributed to Naoki Tsuji.

At least 19 recordsLinked to original sources
PubMed2003

A novel aspartate protease gene, ALP56, is related to morphological features of colorectal adenomas.

BACKGROUND AND AIMS: The recently identified aspartate protease gene ALP56 is up-regulated in human malignant tumors, including colorectal cancers, but the relationship remain unclear between ALP56 gene expression and clinicopathological findings, as well as when genetic alterations in ALP56 occur during the colorectal adenoma-carcinoma sequence. We therefore investigated expression of ALP56 mRNA in various human colorectal tissues. MATERIALS AND METHODS: We examined 18 colorectal adenomas 22 cancers, and 24 adjacent normal mucosal samples from patients undergoing conventional resection or endoscopic mucosal resection. Expression of ALP56 mRNA was determined by quantitative reverse-transcription polymerase chain reaction. RESULTS: Up-regulation of ALP56 gene transcription was observed in both adenomas and cancers compared to normal mucosa. ALP56 expression in exophytic adenomas was significantly greater than in flat adenomas. CONCLUSION: ALP56 may contribute to colorectal adenoma formation and to an exophytic growth pattern in these adenomas.

Adenoma↗
PubMed2003

Regulation of phytochelatin synthesis by zinc and cadmium in marine green alga, Dunaliella tertiolecta.

Although Cd(2+) is a more effective inducer of phytochelatin (PC) synthesis than Zn(2+) in higher plants, we have observed greater induction of PC synthesis by Zn(2+) than Cd(2+) in the marine green alga, Dunaliella tertiolecta. To elucidate this unique regulation of PC synthesis by Zn(2+), we investigated the effects of Zn(2+) and Cd(2+) on the activities of both phytochelatin synthase (PC synthase) and enzymes in the GSH biosynthetic pathway. PC synthase was more strongly activated by Cd(2+) than by Zn(2+), but the difference was not very big. On the other hand, gamma-glutamylcysteine synthetase (gamma-ECS) and glutathione synthetase (GS) were activated by both heavy metals, but their activities were higher in Zn-treated cells than in Cd-treated cells. Dose-dependent stimulation of intracellular reactive oxygen species (ROS) production was observed with Zn(2+), but not Cd(2+) treatment. These results suggest that Zn(2+) strongly promotes the synthesis of GSH through indirect activation of gamma-ECS and GS by stimulating ROS generation. This acceleration of the flux rate for GSH synthesis might mainly contribute to high level PC synthesis.

Aminoacyltransferases↗
PubMed2003

A novel aspartic protease gene, ALP56, is up-regulated in human breast cancer independently from the cathepsin D gene.

Tumor cell invasion requires expression of degradative enzymes such as plasminogen activator, collagenase, and cathepsins. Cathepsin D, a lysosomal aspartic protease produced constitutively in human breast cancer cell lines, also has mitogenic activity in breast cancer cells. Additionally, high cathepsin D expression is associated with increased risk of metastasis in patients with node-negative breast cancer. Recently, a novel aspartic protease gene, ALP56 (aspartic-like protease 56kDa), has been identified. To examine possible interrelationships we quantitated ALP56 mRNA and cathepsin D mRNA in breast cancers using reverse transcription polymerase chain reaction. ALP56 mRNA expression was greater in cancers than in noncancerous tissues (p < 0.0001), as was expression of cathepsin D mRNA. ALP56 gene expression was dose-dependently down-regulated in T-47D breast cancer cells treated with estradiol, while cathepsin D was up-regulated. Expression of ALP56 mRNA in estrogen receptor (ER)-positive breast cancers was less than that in ER-negative cancers, and mRNA expression for ALP56 and cathepsin D did not correlate with one another. Thus ALP56 as well as cathepsin D may be a useful target molecule in breast cancer treatment.

Adult↗
PubMed2002

Enhancement of tolerance to heavy metals and oxidative stress in Dunaliella tertiolecta by Zn-induced phytochelatin synthesis.

The synthesis of phytochelatins (PCs) in a marine alga, Dunalliela tertiolecta, is strongly induced by Zn. Pretreatment of the cells with Zn enhances the tolerance toward toxic heavy metals such as Cd, Hg, Cu, Pb, and arsenate. Moreover, the pretreatment also increases the tolerance toward oxidative stress caused by hydrogen peroxide or paraquat. In vitro analysis shows that PC is a stronger scavenger of hydrogen peroxide and superoxide radical than glutathione. These results suggest that PCs inducibly synthesized by Zn treatment could play a role not only in detoxification of heavy metals but also in mitigation of oxidative stress.

Chelating Agents↗
PubMed2002

Gene expression for suppressors of telomerase activity (telomeric-repeat binding factors) in breast cancer.

Mechanisms regulating telomerase activity and telomere length remain incompletely understood in human breast cancer. We therefore studied gene expression for telomeric-repeat binding factors (TRFs) in relation to telomerase activity, telomere length, and clinicopathologic factors in human breast cancer. Telomerase activity was detected in 65.8% of 38 breast cancers, but none of 16 noncancerous samples. Terminal restriction fragments were longer in noncancerous than in cancerous tissues, but not significantly. Among 8 patients with both cancer and paired noncancerous tissue available for terminal restriction fragments length assay, terminal restriction fragments were shorter in cancers than in paired noncancerous samples in all but one. Significantly more mRNA encoding TRF1 and 2 was detected in noncancerous than in cancer tissues. Additionally, expression of TRF1 and 2 mRNA was significantly higher in cancers without detectable telomerase activity than in cancers showing activity. Expression of these genes tended to show a negative correlation with terminal restriction fragments length, but this was not statistically significant. No correlation was seen between TRF1 or 2 mRNA expression, and clinicopathologic factors except for TRF1 with respect to tumor size and progesterone receptor status. In addition to reactivation of telomerase activity, escape from negative regulation of this activity is needed to maintain telomere length during cell proliferation in breast cancer. Genes encoding telomerase inhibitors might be of value in gene therapy against human breast cancer.

Adenocarcinoma, Mucinous↗
PubMed2002

A role for survivin in radioresistance of pancreatic cancer cells.

Using gene-transduced pancreatic cancer cells, we examined whether survivin expression is directly involved in regulation of radiosensitivity. Ordinarily radiosensitive MIAPaCa-2 cells transduced with wild-type survivin gene (MS cells) proliferated more rapidly than cells transduced with control vector. MS cells were significantly less radiosensitive than control vector-transduced cells. Radiation-induced activity of caspase-3, but not caspase-7, was significantly inhibited in MS cells. On the other hand, transduction of a dominant-negative mutant survivin gene into radioresistant PANC-1 cells augmented radiosensitivity. Further, the radiation-induced increase in caspase-3 activity was enhanced, indicating that survivin function was truly inhibited. These results indicate that survivin expression directly down-regulates radiosensitivity.

Caspase 3↗
PubMed2002

Endogenous reactive oxygen species is an important mediator of miconazole antifungal effect.

We investigated the significance of endogenous reactive oxygen species (ROS) produced by fungi treated with miconazole. ROS production in Candida albicans was measured by a real-time fluorogenic assay. The level of ROS production was increased by miconazole at the MIC (0.125 micro g/ml) and was enhanced further in a dose-dependent manner, with a fourfold increase detected when miconazole was used at 12.5 micro g/ml. This increase in the level of ROS production was completely inhibited by pyrrolidinedithiocarbamate (PDTC), an antioxidant, at 10 micro M. In a colony formation assay, the decrease in cell viability associated with miconazole treatment was significantly prevented by addition of PDTC. Moreover, the level of ROS production by 10 clinical isolates of Candida species was inversely correlated with the miconazole MIC (r = -0.8818; P < 0.01). These results indicate that ROS production is important to the antifungal activity of miconazole.

Antifungal Agents↗
PubMed2002

[Telomerase].

Telomerase, an intranuclear enzyme, binds to telomeres at chromosome ends, helps to elongate telomere length and is closely linked to attainment of cellular immortality, a step in carcinogenesis. Since telomerase activity has been detected in several human tumors and hematopoietic malignancies, this enzyme is thought to be a useful marker for cancer diagnosis. Among the components of telomerase, human telomerase catalytic subunit(hTERT) is the most important regulatory factor for telomerase activity. Therefore, quantitation of hTERT mRNA expression may be a new approach to measuring telomerase activity.

Biomarkers, Tumor↗
PubMed1997

Sulfur-Bridged Cubane-Type Molybdenum-Gallium Clusters with Mo(3)GaS(4)(n)(+) (n = 5, 6) Cores. X-ray Structures of [Mo(3)GaS(4)(H(2)O)(12)](CH(3)C(6)H(4)SO(3))(5).14H(2)O and [Mo(3)GaS(4)(H(2)O)(12)](CH(3)C(6)H(4)SO(3))(6).17H(2)O.

Sulfur-bridged cubane-type molybdenum-gallium clusters [Mo(3)GaS(4)(H(2)O)(12)](5+) (2) and [Mo(3)GaS(4)(H(2)O)(12)](6+) (3) have been synthesized from [Mo(3)S(4)(H(2)O)(9)](4+) (1) and gallium metal and have been isolated as 2(pts)(5).14H(2)O (2.pts) and 3(pts)(6).17H(2)O (3.pts) (Hpts = p-toluenesulfonic acid), whose structures have been characterized by X-ray crystallography. Crystal data for 3.pts: orthorhombic, space group Pca2(1), a = 11.188(1) Å, b = 30.936(4) Å, c = 23.987(2) Å, V = 8301(2) Å(3), Z = 4, D(calcd) = 1.628 g cm(-3), D(obsd) = 1.63 g cm(-3), R (R(w)) = 5.8% (6.3%) for 6102 reflections (I > 3.0sigma(I)). Crystal data for 2.pts: triclinic, space group P&onemacr;, a = 16.406(4) Å, b = 16.743(3) Å, c = 13.173(4) Å, alpha = 90.64 degrees, beta = 98.40(2) degrees, gamma = 89.32(2) degrees, V = 3579.2(14) Å(3), Z = 2, D(calcd) = 1.681 g cm(-3), D(obsd) = 1.68 g cm(-3), R (R(w)) = 6.7% (10.1%) for 7612 reflections (I > 3.0sigma(I)). The Mo-Ga distances (3.pts, 3.60[2] Å; 2.pts, 3.52[2] Å) are much longer than the corresponding Mo-Mo (3.pts, 2.679[7] Å; 2.pts, 2.713[3] Å) distances. At low H(+) concentrations, such as 0.5 M HCl, 2 is stable, and at H(+) concentration higher than 2 M HCl, 2 is oxidized by H(+) to give 3 with evolution of hydrogen gas. Chloride ion plays an important role in the oxidation of 2. Electronic spectra of 3.pts and 2.pts are very similar. Peak positions and epsilon values (lambda(max), nm (epsilon, M(-1) cm(-1))): 3.pts, 762 (447), 550 (204); 2.pts, 760 (404), 548 (205). The cyclic voltammogram of 3 shows three reduction processes (the cathodic peak potentials, E(pc), are -0.83, -1.20, and -1.74 V, respectively), where the first and second processes are quasi-reversible (the anodic peak potentials, E(pa), are -0.55 and -1.00 V, respectively). The reduction current of each process is close to 1:1:3.

Journal Article↗
PubMedDate not supplied

Serum interleukin-18 concentrations in patients with inflammatory bowel disease.

Elevated expression of interleukin (IL)-18 mRNA and protein in intestinal mucosa, attributable to activated monocytes and macrophages in that site, has been reported in patients with inflammatory bowel disease (IBD). However, changes in serum IL-18 concentrations in patients with IBD have not been reported. We measured bioactive IL-18 in serum from patients with IBD, using an enzyme-linked immunosorbent assay (ELISA). Mean serum IL-18 concentrations in 5 patients with Crohn disease (CD) were 400 pg/mL, approximately 1.7 times higher than concentrations in 21 control subjects (p < 0.01). However, serum IL-18 was not increased in patients with ulcerative colitis (UC). These results suggest that like other T-helper type 1 (Th1) cytokines IL-18 may play a key pathogenetic role in Th1-mediated disorders, such as CD. Regulation and expression of IL-18 appears to differ between CD and UC, and serum IL-18 may be a useful clinical marker for CD.

Biomarkers↗
PubMedDate not supplied

Decreased gene expression for telomeric-repeat binding factors and TIN2 in malignant hematopoietic cells.

BACKGROUND: Details of mechanisms regulating telomere length are poorly understood in human hematopoietic cells. MATERIALS AND METHODS: Gene expression for TRFs and TIN2 was studied in hematopoietic cell lines, blood or bone marrow cells from acute leukemia and in normal leukocyte fractions. RESULTS: The telomeres were longest in normal leukocytes, shorter in patient samples and still shorter in malignant hematopoietic cell lines. TRF1 mRNA, TRF2 mRNA and TIN2 mRNA in three myeloblastic cell lines and six lymphoblastic cell lines were significantly less abundant than in the corresponding normal cell types. In patients with acute myeloid leukemia, expression of these gene was also less than in normal cells. In additional studies in culture, HL-60 cells with initially high telomerase activity and low expression of TRF mRNA and TIN2 mRNA differentiated into granulocytic and monocytic cells with low telomerase activity and high expression of these mRNAs. CONCLUSION: In hematopoietic carcinogenesis, gene expression for suppressors of telomerase activity, such as TRF and TIN2, is decreased. These genes might hold promise for gene therapy against cancer.

Adolescent↗
PubMedDate not supplied

Down-regulation of TRF1, TRF2 and TIN2 genes is important to maintain telomeric DNA for gastric cancers.

BACKGROUND: The maintenance of telomeres may be required for long-term proliferation of tumors. Activity of telomerase, a ribonucleoprotein complex that elongates telomeres, has been found in almost all human tumors but not in adjacent normal cells. Several factors which regulate telomere length, TRF1 and 2, TIN2, tankyrase and Rap1, have been identified. TRF1, TRF2 and TIN2 are negative regulators of telomere length, while tankyrase and Rap1 act as positive regulators. In this study, we quantitated the mRNA of these five genes in gastric cancers to clarify the mechanism by which cancer cells maintain telomere length. MATERIALS AND METHODS: The expression of these five genes transcription was determined using a quantitative RT-PCR. RESULTS: TRF1, TRF2 and TIN2 mRNAs were significantly down-regulated in cancers compared to non-cancerous mucosa. Neither tankyrase nor Rap1 was upregulated in cancers. CONCLUSION: Down-regulation of TRF1, TRF2 and TIN2 gene expression may be important to maintain telomeres in gastric cancer.

DNA, Neoplasm↗
PubMedDate not supplied

Overexpression of early growth response-1 as a metastasis-regulatory factor in gastric cancer.

BACKGROUND: To investigate the potential role of a nuclear transcription factor, early growth response-1 (Egr-1), in formation and progression of gastric cancer, we compared its expression in gastric cancers with that in non-cancerous tissues. MATERIALS AND METHODS: Egr-1 mRNA expression was measured using TaqMan RT-PCR. The corresponding protein expression was examined immunohistochemically. RESULTS: Egr-1 mRNA expression was significantly higher in gastric cancer tissues than in normal mucosa (p < 0.0005). These differences were also reflected by protein product expression. Moreover, Egr-1 mRNA expression was higher in cases with metastasis to lymph nodes or remote organs. In cultured gastric cancer cells known to have a high metastatic potential, expression of this mRNA was higher than that of parental cells. CONCLUSION: It was suggested that Egr-1 has a significant role in carcinogenesis and in cancer progression, especially metastasis. Measurement of this mRNA should be useful for evaluation of the metastatic potential of gastric cancer.

Breast↗
PubMedDate not supplied

Endogenous tumor necrosis factor promotes resistance to cellular stresses by inducing the metallothionein-1A gene.

BACKGROUND: Endogenous tumor necrosis factor (enTNF) acts as a resistance factor against anticancer drugs, heat and exogenous TNF via induction of manganous superoxide dismutase (MnSOD) and heat shock protein 72 (HSP72), while the details of interaction with other molecules are not fully understood. We compared mRNA expression of various genes between MIAPaCa-2 human pancreatic cancer cells and M5 cells transduced with nonsecretory-type TNF gene expression vector. MATERIALS AND METHODS: The expression of certain mRNAs between human pancreatic cancer MIAPaCa-2 cells and M5 cells was compared using fluorescent differential display. RESULTS: Of 140 bands obtained by gel electrophoresis, 53 bands showed patterns differing between MIAPaCa-2 and M5 cells. Among these bands, sequence analysis and RT-PCR identified strong mRNA expression for metallothionein-1A, a scavenger of reactive oxygen species, in transduced M5 cells. CONCLUSION: Metallothionein-1A could be induced by enTNF, resulting in resistance against various cellular stresses.

Base Sequence↗