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Biomedical subjects

Hirokuni Taguchi

Publications and source records attributed to Hirokuni Taguchi.

At least 55 records · Page 3Linked to original sources
PubMed2005

Miliary tuberculosis not affecting the lungs but complicated by acute respiratory distress syndrome.

A 61-year-old woman was admitted with fever and headache of 10-day duration. She was found to have anemia, jaundice, and signs of meningitis. The erythrocyte sedimentation rate was increased and the tuberculin skin test was positive. A provisional diagnosis of miliary tuberculosis was made and antituberculous therapy was started, although no miliary lesions were seen on chest radiography. However, her condition rapidly deteriorated with diffuse opacification of both lungs and she died on the 7th hospital day. Postmortem examination revealed miliary tuberculosis in several organs but not in the lungs with acute respiratory distress syndrome accounting for the lung pathology. It should be noted that on rare occasions the lungs may not be involved by miliary tuberculosis.

Bone Marrow↗
PubMed2005

Selective COX-2 inhibitor regulates the MAP kinase signaling pathway in human osteoarthritic chondrocytes after induction of nitric oxide.

The purpose of this study was to examine the effect of cyclooxygenase-2 (COX-2) inhibitors on the mitogen-activated protein (MAP) kinase signaling pathway and synthesis of glucosaminoglycan after nitric oxide (NO) induction in articular human chondrocytes. After NO induction, the cells were divided into three groups that were treated with either ethanol (control); a selective COX-2 inhibitor (Celecoxib), or no additive, and evaluated. There were no differences in the effect of the selective COX-2 inhibitor on mitochondrial membrane potential or Annexin V levels. However, Celecoxib significantly decreased prostaglandin E2 (PGE2) production. Celecoxib also decreased the phosphorylation state of p38 and p44/42 of MAP kinase. The ratio of chondroitin-6 sulfate (C6S)/C4S was increased in response to the exposure to Celecoxib. Celecoxib did not affect apoptosis, but decreased the activation of MAP kinase in osteoarthritic chondrocytes after NO induction. NO-induced OA chondrocytes were associated with the p38 and the p44/42 MAPK signaling pathways, in a pathway that is distinct from PGE2-mediated apoptosis.

Annexin A5↗
PubMed2005

Methylation of the MLH1 gene in hematological malignancies.

Hypermethylation of the MLH1 gene has been described in many kinds of human cancers with microsatellite instability (MSI). However, it is not clear whether the same mechanism occurs in hematological malignancies. Genomic DNA was extracted from 31 patients with adult T-cell leukemia/lymphoma (ATL), 9 patients with acute lymphoblastic leukemia (ALL) who had MSI, and 12 leukemia and lymphoma cell lines with MSI. Aberrant methylation of the MLH1 gene was found in 2/31 (6%) ATL patients, and in 1/12 (8%) cell lines with MSI. MLH1 promoter was not methylated in either of the twelve peripheral blood samples from normal individuals or ALL samples. The MLH1 gene was expressed in the normal peripheral blood samples, but not in the MLH1-methylated cell line KCL22. Demethylation with 5-Azacytidine treatment restored MLH1 expression in the KCL22 cell line. Methylation of the MSH2 gene was not found in any of the samples. Our data show that hypermethylation of the MLH1 gene is occasionally involved in the pathogenesis of hematological malignancies, but is not always associated with MSI.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Role of protein kinase C in expression of granulocyte-colony stimulating factor and granulocyte macrophage-colony stimulating factor in lung cancer cells.

We examine the role of protein kinase C (PKC) pathways in the constitutive expression of granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage-colony stimulating factor (GM-CSF) in lung cancer cells. Two cell lines, OKa-C-1 and MI-4, constitutively produce an abundant dose of G-CSF and GM-CSF. The PKC activator phorbol 12-myristate 13-acetate (PMA) stimulated the production of GM-CSF in a dose-dependent manner and reduced G-CSF in the cell lines. The PKC inhibitor staurosporine had effects opposite to those of PMA in the cell lines. Another PKC activator (4beta-phorbol 12, 13-dibutyrate) and six specific PKC inhibitors (bisindolylmaleimide I, calphostin C, chelerythrine chloride, Gö 6976, PKC inhibitor 19-27, and Ro-32-0432) also worked as well as PMA and staurosporine, respectively. The induction of GM-CSF expression via PKC activation was mediated by the activation of nuclear factor-kappaB. The induction of G-CSF expression via PKC inhibition was mediated by p44/42 mitogen-activated protein kinase and c-Jun N-terminal kinase pathway signaling. GM-CSF may accelerate cell growth and inhibit cell death via PKC activation in the cell lines. G-CSF also seems to reverse growth suppression and cell death induced by PKC inhibition.

Apoptosis↗
PubMed2004

HIV-1 protease inhibitor, ritonavir: a potent inhibitor of CYP3A4, enhanced the anticancer effects of docetaxel in androgen-independent prostate cancer cells in vitro and in vivo.

We previously showed that HIV-1 protease inhibitors (PIs) slowed the proliferation of human myeloid leukemia cells and enhanced their differentiation in the presence of all-trans-retinoic acid. In this study, we found that PIs, including ritonavir, saquinavir, and indinavir, inhibited the growth of DU145 and PC-3 androgen-independent prostate cancer cells as measured by a clonal proliferation assay. Recent studies showed that ritonavir inhibited cytochrome P450 3A4 enzyme (CYP3A4) in liver microsomes. The CYP3A4 is involved in drug metabolism and acquisition of drug resistance. To clarify the drug interaction between ritonavir and other anticancer drugs, we cultured DU145 cells with docetaxel either alone or in combination with ritonavir. Ritonavir enhanced the antiproliferative and proapoptotic effects of docetaxel in the hormonally independent DU145 prostate cancer cells in vitro as measured by the clonogenic soft agar assay and detection of the activated form of caspase-3 and cleavage of poly(ADP-ribose) polymerase using Western blot analysis. Real-time PCR showed that docetaxel induced the expression of CYP3A4 at the transcriptional level, and ritonavir (10(-5) mol/L) completely blocked this induction. An ELISA-based assay also showed that ritonavir inhibited DNA binding activity of nuclear factor kappaB (NFkappaB) in DU145 cells, which is a contributor to drug resistance in cancer cells. Furthermore, combination treatment of docetaxel and ritonavir dramatically inhibited the growth of DU145 cells present as tumor xenografts in BNX nude mice compared with either drug alone. Importantly, docetaxel induced expression of CYP3A4 in DU145 xenografts, and ritonavir completely blocked this induction. Ritonavir also inhibited NFkappaB DNA binding activity in DU145 xenografts. Extensive histologic analyses of the liver, spleen, kidneys, bone marrow, skin, and subcutaneous fat pads from these mice showed no abnormalities. In summary, combination therapy of ritonavir and anticancer drugs holds promise for the treatment of individuals with advanced, drug resistant cancers.

Animals↗
PubMed2004

Effect of serum deprivation on constitutive production of granulocyte-colony stimulating factor and granulocyte macrophage-colony stimulating factor in lung cancer cells.

We previously established 2 lung cancer cell lines, OKa-C-1 and MI-4, which constitutively produce an abundant dose of granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage-colony stimulating factor (GM-CSF). Many other cases with G-CSF or GM-CSF producing tumors have been reported up to the present. However, the biological properties of the overproduction of G-CSF and GM-CSF by tumor cells have not been well known. Several reports demonstrated the presence of an autocrine growth loop for G-CSF and GM-CSF in nonhematopoietic tumor cells. We showed that exogenous G-CSF and GM-CSF stimulated cell growth in a dose-dependent manner in OKa-C-1 and MI-4 cells. We could detect the presence of G-CSF and GM-CSF receptors in both cell lines by RT-PCR analysis. We have previously shown that inflammatory cytokines, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta enhance the expression of G-CSF and GM-CSF in the cell lines. However, the factors that regulate constitutive production of G-CSF or GM-CSF by tumor cells are still unknown well. In our study, we first reported that serum deprivation stimulated constitutive production of G-CSF and GM-CSF by lung tumor cells through activation of nuclear factor (NF)-kappaB and p44/42 mitogen-activated protein kinase (MAPK) pathway signaling. We suggest that G-CSF and GM-CSF constitutively produced by tumor cells could grow tumor itself and rescue tumor cells from the cytotoxicity of serum deprivation.

Carcinoma, Large Cell↗
PubMed2004

Insulin-like growth factor binding protein-3 antagonizes the effects of retinoids in myeloid leukemia cells.

Insulin-like growth factor binding protein-3 (IGFBP-3) can cause growth suppressive and proapoptotic effects on retinoids in many types of cancer cells. However, the expression and effects of IGFBP-3 in myeloid leukemia cells have not been elucidated. In this study, we found no IGFBP-3 expression in the human myeloid leukemia cell lines either at baseline or after stimulation with all-trans retinoic acid (ATRA). Human recombinant IGFBP-3 induced growth arrest and apoptosis of HL-60 and NB4 cells. We have previously identified RXR alpha as a nuclear receptor for IGFBP-3 and have proceeded to examine further the role of this interaction in leukemia cell lines. In signaling assays, IGFBP-3 potently suppressed RAR- and VDR-mediated signaling while enhancing RXR signaling. Interestingly, when IGFBP-3 was administered to these cells in combination with an RAR-selective ligand, the ability of these retinoids to induce differentiation was blunted. On the other hand, IGFBP-3 enhanced the effect of an RXR-selective ligand to induce differentiation of HL-60 and NB4 cells. Further studies showed that IGFBP-3 down-regulated (at the transcriptional level) the retinoid-induced expression of C/EBP epsilon in NB4 cells. Taken together, these results indicate that IGFBP-3 has antiproliferative activity against myeloid leukemia cells; while it enhances signaling through RXR/RXR, it blunts signaling by activated RAR/RXR.

Alitretinoin↗
PubMed2004

Differential gene-expression profiling in the leukemia cell lines derived from indolent and aggressive phases of CD56+ T-cell large granular lymphocyte leukemia.

As a rule, T cell large granular lymphocyte (T-LGL) leukemia runs a chronic clinical course without need for therapy. Some cases, however, progress to an aggressive disease after the indolent clinical stage. The transformation mechanism into a high-grade malignancy has not been well studied. We have established 2 leukemia cell lines, MOTN-1 and PLT-2, derived from the same clone of CD56+ T-LGL leukemia in chronic and aggressive phases, respectively. The paired availability of such cell lines is valuable in biologic and genetic investigation of T-LGL leukemia. We used a microarray containing 406 cDNAs to elucidate alterations of gene expression between the 2 cell lines. We found a number of genes that were differentially expressed: 13 genes with increased expression and 3 genes with reduced expression in PLT-2 cells as compared to MOTN-1 cells. Increased expression of the dek, rac, Op18, CD6, CD58, CD106, Id2, ATF4, IRF5, ELL2 and D6 genes, and reduced expression of the GzmA and GzmK genes were confirmed by real-time quantitative reverse transcription-PCR, whose results paralleled the microarray data. These upregulated genes encode oncoproteins, cell surface antigens including molecules related to T cell proliferation, transcription factors, and a chemokine receptor. The two downregulated genes encode granzymes that play an important role for induction of cell death. These findings suggest that there is differential gene expression in different clinical phases of T-LGL leukemia and these differentially expressed genes would be potential targets for further studies to identify the genes involved in the transformation process of T-LGL leukemia.

CD56 Antigen↗
PubMed2004

Proteasome inhibitor PS-341 down-regulates prostate-specific antigen (PSA) and induces growth arrest and apoptosis of androgen-dependent human prostate cancer LNCaP cells.

Proteasome inhibitor PS-341 induces growth arrest and apoptosis of multiple myeloma (MM) cells via inactivation of nuclear factor kappaB (NF-kappaB) in vitro. In addition, recent clinical studies of PS-341 have demonstrated some objective responses in individuals with relapsed, refractory MM. However, the activity of PS-341 against non-hematological malignancies remains to be fully elucidated. In this study, we found that PS-341 induced growth arrest and apoptosis of androgen-dependent human prostate cancer LNCaP cells in conjunction with markedly up-regulated levels of p21(waf1) and p53. In addition, we found that PS-341 down-regulated both 5alpha-dihydrotestosterone (DHT)- and interleukin-6 (IL-6)-induced expression of prostate-specific antigen (PSA) as measured by western blot analysis. PS-341 down-regulated basal levels of the androgen receptor (AR) in the nucleus; however, it did not affect DHT-induced nuclear translocation of AR in these cells. Reporter assays using a series of promoters of the PSA gene showed that down-regulation of PSA by PS-341 was caused by inhibition of the transcriptional activity of the androgen receptor response element (ARE) in these cells. Taken together, the results indicate that PS-341 induced growth arrest and apoptosis of LNCaP cells by blockade of the AR signaling pathway. The proteasome may be a molecular target for treatment of a variety of cancers including prostate cancer.

Androgens↗
PubMed2004

Proteasome inhibitor PS-341 induces growth arrest and apoptosis of non-small cell lung cancer cells via the JNK/c-Jun/AP-1 signaling.

Proteasome inhibitor PS-341 induces growth arrest and apoptosis of multiple myeloma (MM) cells via inactivation of NF-kappaB in vitro and has afforded some objective responses in individuals with relapsed, refractory MM. However, the activity of PS-341 against non-hematological malignancies remains to be fully elucidated. In this study, we found that PS-341 induced growth arrest and apoptosis of NCI-H520 and -H460 non-small cell lung cancer (NSCLC) cells in conjunction with markedly up-regulated levels of p21(waf1) and p53, and down-regulation of bcl-2 protein in these cells. Also, PS-341 caused phosphorylation of c-Jun NH(2)-terminal kinase (JNK) and c-Jun, and enhanced AP-1/DNA binding activities in these cells as measured by western blotting and enzyme-linked immunosorbent assay (ELISA), respectively. Interestingly, when the JNK/c-Jun/AP-1 signal pathway was disrupted by the JNK inhibitor SP600125, the ability of PS-341 to inhibit the growth of NSCLC cells and to up-regulate the levels of p21(waf1) in these cells was blunted, but the expression of p53 was sustained at a high level, suggesting that the JNK/c-Jun/AP-1 signal pathway might mediate the anti-lung cancer effects of PS-341, with p21(waf1) playing the central role. Thus, PS-341 might be useful for the treatment of individuals with NSCLC.

Antineoplastic Agents↗
PubMed2004

Plumbism.

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Anemia↗