[A case of gastrointestinal stromal tumor of the stomach].
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Adult↗
Biomedical subjects
T Okamoto
Publications and source records attributed to T Okamoto.
[Impairment of host defense via activation of host's proteases by bacterial proteases].
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Animals↗
[Tumor markers for endocrine neoplasms].
Tumor markers for thyroid neoplasms include thyroglobulin, calcitonin, and CEA. Thyroglobulin is particularly useful in discriminating follicular carcinoma from its benign counterparts. The measurement may also be helpful in the postoperative follow-up of patients with either follicular carcinoma or papillary carcinoma. Measuring plasma calcitonin and CEA is essential in the diagnosis and postoperative management of patients with medullary carcinoma. Highly specific genetic tests may become an alternative strategy in cases of familial medullary carcinoma. No specific tumor markers are available for parathyroid carcinoma; however, clinical characteristics provide diagnostic clues.
Biomarkers, Tumor↗
[The minimal residual disease (MRD) in hematological malignancies].
Molecular genetic and cytoimmunological markers have been applied for the detection of minimal residual disease (MRD) in hematological malignancies. These markers include surface markers or rearranged T-cell receptor and immunoglobulin genes in the lymphoid malignancies and fused genes associated with chromosomal translocations such as BCR-ABL in t(9;22) or PML-RAR alpha in t(15;17) in myeloid malignancies. The expression of the WT1 gene is recognized as the universal tumor marker for a wide variety of hematological malignancies. Using these sensitive markers, a tumor cell in 10,000 to 1,000,000 normal cells can be detected. By examining a large number of patients, it has been shown that the MRD in the early phase of chemotherapy has a correlation with the prognosis of childhood ALL. Based on these observations, a new strategy of chemotherapy in which the post-remission therapy is modified based on the MRD results has begun. The amount of tumor cells contaminated in the autologous stem cell grafts in ALL patients might be related to the prognosis. The diagnosis of MRD will be used as an important routine examination in chemotherapy for leukemia/lymphoma patients.
Adult↗
[Effects of erythromycin on the Pseudomonas-induced rabbit diffuse panbronchiolitis model--the improvements in granuloma-like lesions with increasing production of MCP-1].
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Animals↗
[Small lymphocytic lymphoma/chronic lymphocytic leukemia with t(11;14)].
A 83-year-old woman was referred to our hospital because of swollen lymph nodes, marked splenomegaly, and bone marrow abnormality. Histological examination of the lymph nodes revealed characteristic findings for small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). The immunophenotype of the tumor cells was CD5+, 10-, 19+, 20+, 23-, IgM+D+. Interphase fluorescent in situ hybridization (FISH) detected t(11;14), and immunohistochemical studies demonstrated cyclin D1 expression. In both SLL/CLL and mantle cell lymphoma (MCL), the normal counterpart of the tumor cells is thought to be CD5-positive B1 cells. The present case may therefore have been borderline between SLL/CLL and MCL.
Aged↗
Squamous cell carcinoma of the vulva and adjacent lesions treated at Nagoya University Hospital from 1965 to 1997.
Japan has a lower incidence of vulvar squamous cell carcinoma (VSCC) than Western nations. To pin-point the reasons for this, we reviewed biopsy samples from all cases treated at Nagoya University Hospital over the past 33 years in order to investigate the background lesions for VSCC. Two of 36 VSCC patients had adjacent or coexisting lichen sclerosus (LS), 5 had squamous cell hyperplasia (SCH), and 16 had vulvar intraepithelial neoplasia (VIN). There were 8 cases in which these lesions were thought to be the origin of the VSCC, 1 in which keratinizing squamous cell carcinoma (KSC) was seen in LS, 1 in which verrucous SCH was the origin, and 6 in which 4 basaloid carcinoma and 2 warty carcinoma developed from basaloid VIN and warty VIN, respectively. Although 8 other cases of keratinizing or non-keratinizing squamous cell carcinomas (NSC) coexisted with VIN NOS (not otherwise specified), differentiated VIN or basaloid VIN, we could not be histologically certain of the origin. Among 22 VSCC patients tested for HPV DNA, only an 84-year-old woman presenting a histological feature of KSC tested positive by in situ hybridization (ISH). It was considered that LS and SCH had little and VIN considerable capacity to cause the malignancy of VSCC. We surmise that in Japan the majority of squamous cell carcinoma is unrelated to HPV. One reason for the low incidence of VSCC is largely due to race; the homogeneous, monoethnic Japanese population, as well as the few cases of HPV-related VSCC.
Adult↗
Reciprocal modulation of transcriptional activities between HIV-1 Tat and MHC class II transactivator CIITA.
HIV-1 is the etiologic agent of acquired immune deficiency syndrome (AIDS). Functional loss of antigen-presenting cells (APC) in HIV-1 infection is considered to be involved in AIDS pathogenesis. We found that actions of the viral transactivator Tat and the transactivator of MHC class II genes, CIITA, are mutually inhibitory. While Tat inhibited expression of MHC class II genes in APC, overexpression of CIITA inhibited Tat and subsequently HIV-1 replication. This action of Tat appears to be mediated by sequestering the common cofactor, cyclin T1, but not p300 and CBP. These reciprocal actions between Tat and CIITA not only explains the functional impairment of APC in HIV-1 infection but also rationalizes the suppression of HIV-1 virus load by induction of CIITA such as IFN-gamma.
Cell Line↗
Mechanism of superoxide anion generation in the toxic red tide phytoplankton Chattonella marina: possible involvement of NAD(P)H oxidase.
Red tide phytoplankton Chattonella marina is known to produce reactive oxygen species (ROS), such as superoxide anion (O(2)(-)), hydrogen peroxide (H(2)O(2)) and hydroxyl radical (&z.rad;OH), under normal physiological conditions. Although several lines of evidence suggest that ROS are involved in the mortality of fish exposed to C. marina, the mechanism of ROS generation in C. marina remains to be clarified. In this study, we found that the cell-free supernatant prepared from C. marina cells showed NAD(P)H-dependent O(2)(-) generation, and this response was inhibited by diphenyleneiodonium, an inhibitor of mammalian NADPH oxidase. When the cell-free supernatant of C. marina was analyzed by immunoblotting using antibody raised against the human neutrophil cytochrome b558 large subunit (gp91phox), a main band of approximately 110 kDa was detected. The cell surface localization of the epitope recognized with this antibody was also demonstrated in C. marina by indirect immunofluorescence. Furthermore, Southern blot analysis performed on genomic DNA of C. marina with a probe covering the C-terminal region of gp91phox suggested the presence of a single-copy gene coding for gp91phox homologous protein in C. marina. These results provide evidence for the involvement of an enzymatic system analogous to the neutrophil NADPH oxidase as a source of O(2)(-) production in C. marina.
Amino Acid Sequence↗
Direct interaction of p53 with the Y-box binding protein, YB-1: a mechanism for regulation of human gene expression.
The Y-box binding protein, YB-1, belongs to a family of multifunctional proteins which regulate gene expression on both transcriptional and translational levels. The tumor suppressor gene p53 displays growth suppressive properties by regulating gene expression through transcriptional regulation. We now demonstrate that YB-1 directly interacts with p53 using an in vitro pull-down assay. Using immunochemical co-precipitation methods, we also found that the two proteins are bound in vivo. Deletion analysis showed that three independent domains of YB-1, one at the N-terminal and two at the C-terminal, interact with p53. Conversely, a 14 amino acid sequence at the C-terminal of p53 was required for its interaction with YB-1. Gel mobility shift assays showed that the interaction of YB-1 with p53 stimulated the sequence-specific DNA binding of p53 to its consensus sequence. By contrast, this interaction inhibited the binding of YB-1. Using a p53-responsive p21 promoter linked to a reporter gene, it can be shown that antisense expression of YB-1 inhibits the induction of this promoter by p53 in transient transfection assays. These findings delineate a straightforward mechanism for gene expression through p53-YB-1 interaction.
CCAAT-Enhancer-Binding Proteins↗
Akt-mediated survival of oligodendrocytes induced by neuregulins.
Neuregulins have been implicated in a number of events in cells in the oligodendrocyte lineage, including enhanced survival, mitosis, migration, and differentiation. At least two signaling pathways have been shown to be involved in neuregulin signaling: the phosphatidylinositol (PI)-3 kinase and the mitogen-activated protein kinase pathways. In the present studies, we examined the signaling pathway involved in the survival function of heregulin, focusing on heregulin-induced changes in Akt activity in cultured glial cells, and the consequences of Akt activation in cells in the oligodendrocyte lineage. Heregulin binds erbB receptors, and in our studies, primary cultures of both oligodendrocyte progenitor cells and differentiating oligodendrocytes expressed erbB2, erbB3, and erbB4 receptors. In C6 glioma cells and primary cultures of oligodendrocytes, heregulin induced time- and dose-dependent Akt phosphorylation at Ser(473) in a wortmannin-sensitive manner. To investigate further the signaling pathway for heregulin in glial cells, BAD was overexpressed in C6 glioma cells. In these cells, heregulin induced phosphorylation of BAD at Ser(136). Apoptosis of oligodendrocyte progenitor cells induced by growth factor deprivation was effectively blocked by heregulin in a wortmannin-sensitive manner. Overexpression of dominant negative Akt but not of wild-type Akt by adenoviral gene transfer in primary cultures of both oligodendrocytes and their progenitors induced significant apoptosis through activation of the caspase cascade. The present data suggest that the survival function of heregulin is mediated through the PI-3 kinase/Akt pathway in cells in the oligodendrocyte lineage and that the Akt pathway may be quite important for survival of cells in this lineage.
Androstadienes↗
d-Aspartate in a prolactin-secreting clonal strain of rat pituitary tumor cells (GH(3)).
d-Aspartate (d-Asp) is found in prolactin (PRL)-containing cells of the rat anterior pituitary gland [Lee et al., Brain Res. 838, 193-199, 1999]. In order to determine whether d-Asp is actually produced by the anterior pituitary gland and whether it plays a physiological role in PRL function, a PRL-secreting clonal strain of rat pituitary tumor cells (GH(3)) was employed in this study. HPLC analysis and immunocytochemical staining detected the presence and synthesis of d-Asp in the cytoplasm of these cells. In addition, thyrotropin-releasing hormone-stimulated PRL secretion was increased in a dose-dependent fashion by d-Asp from these cells. These results suggest that the anterior pituitary gland synthesizes d-Asp and that d-Asp acts as a messenger in this gland.
Animals↗
Inhibition of anti-Fas antibody-induced hepatitis by aminoguanidine in mice.
Aminoguanidine is an inhibitor of inducible nitric oxide synthase (iNOS) and is of potential clinical usefulness. Treatment of mice with anti-Fas antibodies (150 microg/kg, i.v.) induced elevation of plasma alanine aminotransferase activity at 4 h and this elevation was inhibited by pretreatment of mice with aminoguanidine (3, 10 and 30 mg/kg, i.p.). The anti-Fas antibody-induced elevation of caspase-3 activity was inhibited by aminoguanidine (30 mg/kg, i.p.), but the addition of aminoguanidine to the cytosol up to 10(-4) M did not inhibit the caspase-3 activity in vitro. Thus, aminoguanidine prevents anti-Fas antibody-induced hepatitis by affecting the apoptotic pathway upstream of caspase-3 activation.
Animals↗
Identification and characterization of TMEFF2, a novel survival factor for hippocampal and mesencephalic neurons.
We have identified a novel mammalian gene, TMEFF2, that encodes a putative transmembrane protein containing two follistatin-like domains and one epidermal growth factor (EGF)-like domain. The TMEFF2 gene is predominantly expressed in the brain. In situ hybridization analysis revealed that TMEFF2 is widely expressed in the brain, including hippocampal cornu ammonis, dentate gyrus, and substantia nigra pars compacta. We evaluated the survival effect of TMEFF2 using primary cultured neurons from several regions of fetal rat brain following treatment with a recombinant TMEFF2 protein fragment consisting of the putative extracellular domain. TMEFF2 increased survival of neurons from the hippocampus and midbrain, but not from the cerebral cortex, indicating that the survival effects of TMEFF2 are specific to certain cell types. Recombinant TMEFF2 also promoted survival of mesencephalic dopaminergic neurons. Together, these findings suggest that TMEFF2 may be a novel survival factor for hippocampal and mesencephalic, but not for cortical, neurons.
Amino Acid Sequence↗
Cimetidine inhibits cancer cell adhesion to endothelial cells and prevents metastasis by blocking E-selectin expression.
Although the beneficial effect of cimetidine on survival in cancer has been clinically demonstrated in colorectal cancer patients, the mode of action of cimetidine has not been elucidated. In this report, we have demonstrated for the first time that cimetidine can block the adhesion of a colorectal tumor cell line to the endothelial cell monolayer in cell culture and that it can suppress the metastasis of the tumor cell in a nude mouse model. We also demonstrated that these antimetastasis effects of cimetidine might occur through down-regulation of the cell surface expression of E-selectin on endothelial cells, a ligand for sialyl Lewis antigens on tumor cells. We found that the cimetidine-mediated down-regulation of E-selectin did not involve down-regulation of E-selectin mRNA or blocking of the nuclear translocation of nuclear factor kappaB, a transcriptional activator of E-selectin gene expression. Because two other histamine type 2 receptor antagonists, famotidine and ranitidine, did not show any similar effect, these actions of cimetidine probably do not occur via blocking of the histamine receptor. These observations support the idea that cancer metastasis can be blocked by cimetidine administration through blocking the adhesion of tumor cells to the endothelium when an interaction between E-selectin and sialyl-Lewis antigens plays a role.
Animals↗
Inhibition of the RNA-dependent transactivation and replication of human immunodeficiency virus type 1 by a fluoroquinoline derivative K-37.
Human immunodeficiency virus type 1 (HIV-1) is unique in that it encodes its own transcriptional activator Tat, which specifically binds to the viral mRNA sequence TAR (transactivation response) element and activates viral transcription at the step of elongation as well as initiation. We recently reported that fluoroquinoline derivatives inhibited HIV-1 replication most likely by blocking viral transcription. In this report, we investigated the mechanism of action of one such compound 7-(3, 4-dehydro-4-phenyl-1-piperidinyl)-1, 4-dihydro-6-fluoro-1-methyl-8-trifluoromethyl-4-oxoquinoline-3-carbox ylic acid (K-37). We demonstrated that K-37 inhibited not only Tat but also other RNA-dependent transactivators. No effect was observed with DNA-dependent transactivators such as p65 (NF-kappaB) and Gal4VP16. Moreover, K-37 did not inhibit carboxyl-terminal domain (CTD)-kinase activities of CDK-activating kinase (CAK) and positive transcription elongation factor b (P-TEFb), which are known to be involved in Tat-mediated transactivation at the step of transcriptional elongation. It is suggested that RNA-mediated transactivation may involve a common unknown factor to which K-37 directly interacts. Since K-37 did not appear to block DNA-mediated transactivation and thus did not show strong nonspecific cytotoxicity as reported previously, K-37 and its derivative compounds are considered to be feasible candidates for a novel AIDS therapy.
Animals↗
Expression of facilitative glucose transporter 1 mRNA in colon cancer was not regulated by k-ras.
The expression of facilitative glucose transporter isoforms in colon adenocarcinoma and the possible role of k-ras in inducing GLUT (glucose transporter) mRNA were studied. RT-PCR demonstrated GLUT2 and GLUT3 expression in 100% of the ten normal colon mucosa samples but detected no GLUT1 mRNA. By contrast, GLUT1 mRNA was detected in all 20 (100%) colon cancer samples examined. GLUT4 mRNA was not detected in either normal mucosa or colon cancer tissues. Semiquantitative PCR demonstrated equal amounts of GLUT2 and GLUT3 mRNA in both normal mucosa and colon cancer samples. A point mutation in codon 12 of k-ras was detected in only six of the 20 (30%) colon cancer samples. Thus, a major difference between normal colon epithelia and colon cancer was the acquisition of GLUT1 expression, which was unlikely to have been induced by a point mutation in codon 12 of k-ras.
Adenocarcinoma↗
Aminoguanidine prevents concanavalin A-induced hepatitis in mice.
Aminoguanidine is an inhibitor of the inducible form of nitric oxide synthase (iNOS). In the present study, the effect of aminoguanidine on concanavalin A-induced hepatitis was examined. Treatment of mice with concanavalin A (10 mg/kg, i.v.) induced interferon-gamma and iNOS mRNA expression in the liver before the elevation of plasma alanine aminotransferase activity. Immunohistochemical study showed the induction of iNOS protein expression in the area of necrosis. Aminoguanidine (1, 3 and 10 mg/kg, i.p.) inhibited the concanavalin A-induced elevation of alanine aminotransferase activity. Aminoguanidine (10 mg/kg, i.p.) did not inhibit concanavalin A-induced interleukin-2, interferon-gamma, tumor necrosis factor-alpha or iNOS mRNA expression in the liver. The plasma nitrite/nitrate level was elevated at 6 and 24 h after concanavalin A treatment. The elevation of nitrite/nitrate was inhibited by aminoguanidine (10 mg/kg, i.p.). From these results, we conclude that nitric oxide formed by iNOS may be involved in the development of concanavalin A-induced hepatitis.
Alanine Transaminase↗