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Biomedical subjects

Hirokuni Taguchi

Publications and source records attributed to Hirokuni Taguchi.

At least 91 records · Page 5Linked to original sources
PubMed2003

Frameshift mutations in caspase-5 and other target genes in leukemia and lymphoma cell lines having microsatellite instability.

Microsatellite instability (MSI) was examined in 49 lymphoid leukemia/lymphoma cell lines. Frameshift mutations within eight MSI target genes were analyzed in the 12 cell lines and nine childhood acute lymphoblastic leukemia (ALL) samples with MSI. Six cell lines (50%) showed mutations within the coding repeats of the BLM, caspase-5, TCF-4, and PTEN genes. No mutations were identified in the nine childhood ALL samples with MSI. This is the first report that describes mutations of these genes in hematological malignancies. Mutations, presumably caused by an abnormality of the DNA repair genes, may be selected for during the establishment of cell lines.

Adenosine Triphosphatases↗
PubMed2003

Cyclooxygenase-2 inhibitor NS-398 suppresses cell growth and constitutive production of granulocyte-colony stimulating factor and granulocyte macrophage-colony stimulating factor in lung cancer cells.

We previously established two lung cancer cell lines, OKa-C-1 and MI-4, which constitutively produce abundant granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage-colony stimulating factor (GM-CSF). Inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta stimulated the expression of G-CSF, GM-CSF, and cyclooxygenase (COX)-2 in the two cell lines. It is known that increased COX-2 activity promotes tumor growth and induces G-CSF and GM-CSF expression in non-malignant cells, and that selective COX-2 inhibitors inhibit the growth of some types of malignant cells. Therefore, we hypothesized that inhibition of COX-2 activity might suppress constitutive production of G-CSF or GM-CSF in addition to reducing the growth of malignant cells. We confirmed that the selective COX-2 inhibitor, NS-398 suppressed the constitutive production of G-CSF and GM-CSF, and the cell growth in both OKa-C-1 and MI-4 cell lines. Prostaglandin E2 (PGE2) reversed the inhibitions of G-CSF and GM-CSF expression, as well as cell growth, by NS-398. This result confirms that the effects of NS-398 are based on the inhibition of COX activity. Some studies have indicated that nuclear factor kappa B (NF-kappaB) or MAPK (mitogen-activated protein kinase) activation is related to upregulation of G-CSF, GM-CSF or COX-2 expression in some types of cells. Therefore, we examined if the actions of NS-398 might be mediated by the MAP kinase pathway or NF-kappaB activity in OKa-C-1 and MI-4 cells. We found that NS-398 inhibits G-CSF and GM-CSF production and cell growth through an extracellular signal-regulated kinase kinase (MEK) signaling pathway in these cell lines. The prognosis of non-small cell lung cancer showing G-CSF gene expression is significantly worse. G-CSF overproduction by tumor cells is observed at an advanced clinical stage. Our findings imply that a COX-2 inhibitor might improve the prognosis of patients with lung cancer through the reduction of G-CSF or GM-CSF.

Cell Division↗
PubMed2003

PC-SPES: a potent inhibitor of nuclear factor-kappa B rescues mice from lipopolysaccharide-induced septic shock.

Septic shock is the most common cause of death in intensive care units, and no effective treatment is available at present. Lipopolysaccharide (LPS) is the primary mediator of Gram-negative sepsis by inducing the production of macrophage-derived proinflammatory cytokines, in which activation of nuclear factor-kappaB (NF-kappaB) plays an important role. PC-SPES is an eight-herb mixture active against a variety of malignancies, including prostate cancer and leukemia. In this study, we demonstrated that PC-SPES inhibited the LPS-induced NF-kappaB reporter activity in RAW264.7 macrophages. Electrophoretic mobility shift assay showed that PC-SPES inhibited the binding of NF-kappaB to specific DNA sequences; however, it did not affect either degradation of inhibitory kappaBalpha or nuclear translocation of NF-kappaB. Also, we explored the effect of PCSPES on LPS-induced mitogen-activated protein (MAP) kinase signaling; PC-SPES did not affect LPS-induced phosphorylation of MAP kinases, including c-Jun NH2-terminal kinase, p38, and extracellular signal-regulated kinase 1/2. Moreover, PC-SPES decreased the production of proinflammatory cytokines and inducible enzymes, such as tumor necrosis factor (TNF) alpha, interleukin (IL)-1beta, IL-6, cyclooxygenase-2, as well as inducible nitric-oxide synthase in RAW264.7 macrophages and peritoneal macrophages from C57BL/6 mice after the cells were stimulated by either LPS or LPS and interferon-gamma. Furthermore, PC-SPES rescued C57BL/6 mice from death caused by LPS-induced septic shock in conjunction with decreased serum levels of TNFalpha and IL-1beta. Together, PC-SPES is a potent inhibitor of NF-kappaB and might be useful for the treatment of sepsis and inflammatory diseases.

Animals↗
PubMed2003

[A case of pulmonary actinomycosis with a unique finding in the chest MR image].

A 57-year old man, who was complaining of a productive cough and right shoulder pain, was admitted to our hospital because of an irregularly shaped mass located at rt. S1 on a chest radiograph. Bronchoscopy revealed no evidence suggesting lung cancer or any specific infection, either pathologically or microbiologically. CT-guided biopsy revealed changes resembling lymphocytic or plasmocytic interstitial pneumonitis with thickening of the alveolar septum and with accumulations of mononuclear cells and plasma cells, indicating the proliferation of bronchus-associated lymphoid tissue (BALT system). Since no definitive diagnosis was considered possible, a right upper lobectomy was performed. Histopathologic examination of tissue from the right upper lobe revealed sulfur granules and branching Gram-positive filamentous bacteria, and the condition was pathologically diagnosed as pulmonary actinomycosis. In the center of the mass lesion, the patient's chest MRI showed a very small area with a low signal intensity in T1- and a high signal in T2-weighted images, which suggested an accumulation of fluid in the actinomycotic abscess. As detailed MR findings in this condition have not been well described in the literature, the MRI evidence seen in this case may be useful for the diagnosis of actinomycosis.

Actinomycosis↗
PubMed2003

Identification of a new GLC1A mutation in a sporadic, primary open-angle glaucoma in Japan.

Glaucoma is a major cause of blindness characterized by progressive degeneration of the optic nerve and elevated intraocular pressure. Recent studies have revealed a genetic basis for a substantial proportion of cases of familial primary open-angle glaucoma (POAG) and the gene causing the abnormality has been identified. Sequence variations that meet the criteria for a probable disease-causing mutation have been found in the American and European populations. In this study, we examined 58 cases of sporadic glaucoma from Japan to clarify the relationship between the mutations of the GLC1A gene and sporadic glaucoma in Japan. We have examined 33 POAG, 17 primary closed-angle glaucomas, 6 normal-tension glaucomas and 2 steroid-induced glaucomas for mutation of the GLC1A gene using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and direct DNA sequencing studies. We identified a previously unreported GGT right curved arrow GAT transition at codon 451 in exon 3, resulting in a glycine to asparagine substitution in one POAG patient. No other mutations of the GLC1A gene were found in other types of glaucoma. These findings further emphasize the importance of GLC1A mutation in the development of POAG.

Asian People↗
PubMed2003

Oridonin induces growth inhibition and apoptosis of a variety of human cancer cells.

PC-SPES is an eight herbal mixture that was shown to have activity against prostate cancer. Recently, we purified oridonin from Rabdosia rubescens, one component of PC-SPES, by high performance liquid chromatography (HPLC). The ability of oridonin to inhibit the proliferation of cancer cells was examined by MTT assay. Oridonin effectively inhibited the proliferation of a wide variety of cancer cells including those from prostate (LNCaP, DU145, PC3), breast (MCF-7, MDA-MB231), non-small cell lung (NSCL) (NCI-H520, NCI-H460, NCI-H1299) cancers, acute promyelocytic leukemia (NB4), and glioblastoma multiforme (U118, U138) with ED50s ranging from 1.8 to 7.5 micro g/ml. TUNEL assay and cell cycle analysis showed that oridonin induced apoptosis and G0/G1 cell cycle arrest in LNCaP prostate cancer cells. In addition, expression of p21waf1 was induced in LNCaP and NCI-H520 cells in a p53-dependent manner. Interestingly, when p53 was suppressed by over-expression of E6 from human papilloma virus type 16 (HPV-16), these cells lost their sensitivity to oridonin-induced growth inhibition and apoptosis. Taken together, oridonin inhibited the proliferation of cancer cells via apoptosis and cell cycle arrest with p53 playing a central role in several cancer types which express the wild-type p53 gene. Oridonin may be a novel, adjunctive therapy for a large variety of malignancies and probably represents one of the major, active components of PC-SPES.

Apoptosis↗
PubMed2003

PC-SPES decreases proliferation and induces differentiation and apoptosis of human acute myeloid leukemia cells.

PC-SPES is an eight herbal mixture which has been shown to be active against prostate cancer cells in vitro as well as in patients. In this study, we discovered that it has anti-leukemia activity. HL-60, NB4, U937 and THP-1 human acute myeloid leukemia cells were cultured in the presence of various concentrations of PC-SPES (0.06-0.5 micro l/ml) for 4 days, and cell numbers were counted by Trypan blue exclusion. PC-SPES inhibited proliferation of these cells with an ED50 of 0.17, 0.09, 0.18, 0.32 micro l/ml, respectively. In clonogenic assay, PC-SPES inhibited growth of HL-60 cells (ED50, 0.043 micro l/ml). On the other hand, PC-SPES (0.1 micro l/ml) stimulated growth of normal myeloid committed stem cells (CFU-GM) by 1.4-fold of control (p=0.03). Anti-leukemia effects also occurred against freshly isolated leukemia cells from acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients. Interestingly, when PC-SPES was combined with ATRA, the antiproliferative effect was markedly enhanced. For example, PC-SPES (0.125 micro l/ml) or ATRA (10(-8) mol/l) inhibited growth of HL-60 cells after 4 days of culture, by approximately 40 and 30%, respectively; simultaneous treatment with both, suppressed growth by 80%. In addition, PC-SPES induced differentiation of HL-60 and NB4 cells, as measured by expression of CD11b and reduction of NBT. ATRA synergistically enhanced this activity. For example, either PC-SPES (0.5 micro l/ml) or ATRA (10(-8) mol/l) induced 23 and 18% of HL-60 cells, respectively to express CD11b on day 2 of culture; and when both were combined, 60% of HL-60 cells were stimulated to express CD11b antigen. Furthermore, PC-SPES (0.5 micro l/ml) produced apoptosis of HL-60 and NB4 cells, as measured by TUNEL assay, with 17% of HL-60 cells and 52% of NB4 cells becoming apoptotic on their third day of culture. Importantly, PC-SPES stimulated expression of the novel myeloid specific transcription factor C/EBPepsilon in HL-60 and NB4 cells. Taken together, PC-SPES inhibits growth and induces differentiation and apoptosis of myeloid leukemia cells, and enhances the antiproliferative and prodifferentiative effects of ATRA on these cells. PC-SPES might be useful with ATRA for treatment of patients with acute promyelocytic leukemia (APL), and it could have a role in other types of cancers including MDS.

Antineoplastic Agents, Phytogenic↗
PubMed2003

PC-SPES: Molecular mechanism to induce apoptosis and down-regulate expression of PSA in LNCaP human prostate cancer cells.

PC-SPES is an eight-herbal mixture which has activity against prostate cancer cells and can reduce the serum level of prostate specific antigen (PSA) in more than 80% of individuals with prostate cancer. We conducted this study to begin to clarify the molecular mechanism by which PC-SPES inhibited the growth of prostate cancer cells and down-regulated expression of PSA. Western blot analysis, luciferase reporter assay using a variety of promoters of the PSA gene and the isolated androgen receptor response elements (ARE), as well as electrophoretic mobility shift assay (EMSA) were employed to study the effect of PC-SPES on DHT-induced expression of PSA in LNCaP androgen-dependent human prostate cancer cells. Also, Western blot analysis and luciferase reporter assay using 12-0-tetradecanoylphorbol-13-acetate response elements were employed to study the ability of PC-SPES to activate the c-Jun NH2-terminal kinase (JNK)/c-Jun/AP-1 signal pathway in these cells. Reporter studies showed that PC-SPES inhibited DHT-induced PSA promoter/enhancer-luciferase activity via inhibition of ARE transcriptional activity. Western blot analysis showed that PC-SPES down-regulated DHT-induced expression of PSA without decreasing DHT-induced nuclear level of AR. EMSA demonstrated that PC-SPES inhibited the binding of DHT-activated AR to ARE. Moreover, we found that PC-SPES phosphorylated JNK, increased levels of phosphorylated and unphosphorylated forms of c-Jun, and enhanced AP-1 transcriptional activity in LNCaP cells. Interestingly, when LNCaP cells were stably tranfected with the dominant negative JNK binding domain (JBD) of JNK-interacting protein-1 (JIP-1), these cells no longer underwent apoptosis and growth inhibition in the presence of PC-SPES. But, PC-SPES still decreased levels of PSA in the LNCaP-JIP-1 cells. Taken together, PC-SPES inhibited binding of DHT-activated AR to AREs of PSA gene resulting in down-regulation of ARE transcriptional activity and expression of PSA, and this occurred independently of the JNK/c-Jun/AP-1 signal pathway. Also, PC-SPES activated the JNK/c-Jun/AP-1 signal pathway resulting in growth arrest and apoptosis of prostate cancer cells.

Antineoplastic Agents, Phytogenic↗
PubMed2003

[Pancreatic metastasis from lung cancer: report of an autopsy case].

A 69 year-old man with abnormal lung shadows in the right lung field was admitted to our hospital. A chest computed tomography (CT) scan showed a lung tumor with hilar and mediastinal lymph node swelling. A CT scan of the abdomen demonstrated a solitary pancreatic head tumor with a diameter of 3 cm. Pathological examination of a transbronchial biopsy specimen revealed squamous cell carcinoma (SCC) of the lung. Since obstructive jaundice had progressed rapidly, the patient received endoscopic nasobiliary drainage (ENBD) and stent-drainage therapy prior to chemotherapy using gemcitabine. However, he died 4 months later of respiratory failure and systemic candidiasis associated with progression of the cancer. An autopsy was performed, and microscopic and immunohistochemical examination revealed that the pancreatic tumor was a metastasis from lung cancer. To our knowledge, obstructive jaundice due to pancreatic metastasis from lung SCC, especially that preceding the advent of a clinical manifestation of primary lung cancer, has rarely been reported.

Aged↗
PubMed2002

A novel t(16;20)(q22;p13) in polycythemia vera.

We report a patient with polycythemia vera whose bone marrow cells carried a novel t(16;20)(q22;p13) as detected by karyotype analysis using G- and Q-banding techniques. The reciprocal translocation was confirmed by fluorescence in situ hybridization (FISH) using DNA libraries of chromosomes 16 and 20. To our knowledge, t(16;20)(q22;p13) has not been reported previously. The core binding factor beta (CBFbeta) gene located on 16q22 is known to be frequently involved in acute myelocytic leukemia. On the other hand, the 20p13 locus contains a gene encoding protein kinase CK2alpha, which is closely related to cell proliferation and cell cycle regulation. The t(16;20)(q22;p13) may be one of the cytogenetic aberrations in myeloproliferative disorders, and therefore, our observation warrants further studies on a possible involvement of the genes resulting from this translocation.

Bone Marrow Cells↗
PubMed2002

Epstein-Barr virus (EBV)-positive pyothorax-associated lymphoma (PAL): chromosomal integration of EBV in a novel CD2-positive PAL B-cell line.

Pyothorax-associated lymphoma (PAL) is a clinico-pathological entity arising in the pleural cavity of patients with long-standing inflammatory pyothorax. PAL is closely associated with Epstein-Barr virus (EBV), but how this virus contributes to the development of the lymphoma is unknown. We have successfully obtained a novel EBV-infected PAL cell line, designated Pal-1. The cell line and its source coexpressed CD2 and CD20 molecules, but other representative B- and T-cell markers such as CD1, CD3, CD5, CD7, CD10 and CD19 were not found. The B-cell origin of Pal-1 cells was proven by rearrangement of the immunoglobulin heavy- and light-chain genes without rearranged T-cell receptor genes. Both the cell line and primary tumour cells carried monoclonal EBV genome. Although EBV genome is known to be maintained as circular extrachromosomal DNA, neither circular nor linear extrachromosomal EBV DNA was detectable in Pal-1 cells by in situ lysis gel analysis. Fluorescence in situ hybridization demonstrated viral integration at a marker chromosome mostly consisting of the centromere region of chromosome 1. The viral integration event may enhance a chromosomal instability at the insertion site. This cell line represents the first example of EBV integration in PAL and could enable the study of the potential role of integrated viral infection in the development of PAL as well as mechanism of the aberrant phenotype expression.

Aged↗
PubMed2002

Genetic polymorphisms in the tumour necrosis factor locus in childhood acute lymphoblastic leukaemia.

Genetic polymorphisms in the tumour necrosis factor (TNF) locus influence the outcome of non-Hodgkin's lymphoma (NHL). We investigated whether these polymorphisms might contribute to the clinical course of childhood acute lymphoblastic leukaemia (ALL). Genomic DNA from 214 childhood ALL patients was analysed. Patients with a high-risk haplotype were older than patients with low-risk haplotype (P = 0.024). No statistically significant associations were found between TNF haplotype and sex, WBC counts, central nervous system involvement, immunophenotype, response to chemotherapy, and event-free survival. These data suggest that genetic polymorphisms in the TNF locus have a limited effect on the outcome of childhood ALL.

Age Factors↗
PubMed2002

Establishment and characterization of a new lung cancer cell line (MI-4) producing high levels of granulocyte colony stimulating factor.

We established a human lung cancer cell line, MI-4 from the pleural effusion of a 69-year-old male with advanced large cell undifferentiated carcinoma of the lung complicated by leukocytosis. The culture supernatant of MI-4 contained high levels of granulocyte colony stimulating factor (G-CSF). The intracellular localization of the G-CSF was identified by immunocytochemistry. Reverse transcription-polymerase chain reaction (RT-PCR) revealed G-CSF mRNA expression in this cell line. The cell line was successfully transplanted into nude mice. The transplanted nude mice also showed leukocytosis with a high serum G-CSF level. Southern blot analysis did not show amplification or rearrangement of the G-CSF gene in MI-4 cells. Spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) analyses revealed that this cell line has an additional chromosome 17 attached to a segment of chromosome 10 besides two intact chromosomes 17, and that each of these three chromosomes 17 has a G-CSF gene on chromosome 17q. Inflammatory cytokines, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, significantly enhanced G-CSF expression at both the protein and mRNA levels in MI-4. However, these cytokines did not stimulate the growth of MI-4 cells, regardless of abundant G-CSF production. TNF-alpha rather suppressed it, in a dose-dependent manner. Exogenous recombinant human G-CSF and anti-G-CSF antibody did not promote or inhibit the growth of MI-4 cells at any concentration examined. In addition, RT-PCR analysis did not show G-CSF receptor mRNA expression. These results suggest that this cell line does not have an autocrine growth loop for G-CSF. This cell line should be very useful for understanding the biological activity of G-CSF in G-CSF-overproducing lung cancer.

Aged↗