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M Koike

Publications and source records attributed to M Koike.

At least 127 records · Page 7Linked to original sources
PubMed1999

Ovarian cancer: loss of heterozygosity frequently occurs in the ATM gene, but structural alterations do not occur in this gene.

Ataxia-telangiectasia is a multisystem recessive disease characterized clinically by cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency, sensitivity to radiomimetic agents and an increased predisposition to cancer. This pleiotropic disorder is caused by mutations in the ATM gene, which is located at the human chromosomal region 11q23. Loss of heterozygosity (LOH) at 11q22-q23 is a frequent event in ovarian cancer, suggesting the presence of a tumor suppressor gene in this region. We have found that LOH in the ATM gene occurred in 44% of informative cases in a series of 22 primary ovarian tumors. LOH of this region occurred at the same frequency during the advanced stages (III-IV; 3/9, 33%) as in the early stages (I-II; 4/13, 31%) of ovarian cancer. To investigate the role of ATM in ovarian cancer, we used a PCR-based single-strand conformation polymorphism assay for mutation detection of the entire coding sequence of the ATM gene (65 exons) in 22 ovarian tumors. No somatic alterations of the ATM gene were found in these ovarian cancer samples including those with LOH present in the ATM gene. Our study has identified a region (11q23) which probably contains a frequently altered tumor suppressor gene in ovarian cancer, and this gene does not appear to involve the coding sequences of the ATM gene.

Adenocarcinoma↗
PubMed1999

Cytogenetic mapping of 31 functional genes on chicken chromosomes by direct R-banding FISH.

Using direct R-banding fluorescence in situ hybridization, we determined the location of 31 functional genes on chicken chromosomes. Replication R-banded chromosomes were obtained by synchronizing splenocyte cultures with excessive thymidine, followed by BrdU treatment. Thirty-one functional genes were directly localized to banded chicken chromosomes using genomic DNA and cDNA fragments as probes. The possibility of conserved linkage homology between chicken and human chromosomes was demonstrated for seven chicken chromosome regions (1p, 1q, 2q, 4p, 4q, and 5q).

Animals↗
PubMed1999

Differential subcellular localization of DNA-dependent protein kinase components Ku and DNA-PKcs during mitosis.

The Ku protein is a complex of two subunits, Ku70 and Ku80. Ku plays an important role in DNA-PKcs-dependent double-strand break repair and V(D)J recombination, and in growth regulation, which is DNA-PKcs-independent. We studied the expression and the subcellular localization of Ku and DNA-PKcs throughout the cell cycle in several established human cell lines. Using immunofluorescence analysis and confocal laser scanning microscopy, we detected Ku70 and Ku80 in the nuclei in interphase cells. In mitotic cells (1) most of Ku protein was found diffused in the cytoplasm, (2) a fraction was detected at the periphery of condensed chromosomes, (3) no Ku protein was present in the chromosome interior. Association of Ku with isolated chromosomes was also observed. On the other hand, DNA-PKcs was detected in the nucleus in interphase cells and not at the periphery of condensed chromosomes during mitosis. Using indirect immunoprecipitation, we found that throughout the cell cycle, Ku70 and Ku80 were present as heterodimers, some in complex with DNA-PKcs. Our findings suggest that the localization of Ku at the periphery of metaphase chromosomes might be imperative for a novel function of Ku in the G(2)/M phase, which does not require DNA-PKcs.

Antigens, Nuclear↗
PubMed1999

Significance of thymidine phosphorylase as a marker of protumor monocytes in breast cancer.

Tumor-associated monocytic cells (TAMs) are a major component of the stroma responsible for tumor formation. TAMs generate various kinds of mediators for their function, one of which is thymidine phosphorylase (TP). TP is an angiogenic enzyme that is known to be up-regulated in tumor tissues. Here, we focused on the clinical implication of TP expression in TAMs by studying 229 primary breast carcinoma tissues. Immunohistochemical analysis demonstrated that monocytic TP+ tumors had a significantly worse prognosis than did monocytic TP- tumors (P < 0.01, log-rank test). A multivariate analysis confirmed that monocytic TP status provided an independent prognostic value (P < 0.0001). Furthermore, of interest was that monocytic TP status could categorize the CD68+ patients, who had an extensive accumulation of CD68+ TAMs, into two subgroups with strikingly contrasting prognoses: a good prognostic monocytic TP- group and a poor prognostic monocytic TP+ group. This indicates that there are both antitumor and protumor types of TAM. Subanalysis showed that microvessel density was significantly increased in CD68+/monocytic TP+ tumors compared with CD68+/monocytic TP- tumors. Experimentally, TAMs are known to function in diverse manners, antitumor and protumor; however, little is known about clinically recognizable markers to characterize the TAMs in histological sections. TP might be such a marker, which would be useful for identifying the character of TAMs, particularly the protumor phenotype.

Adult↗
PubMed1999

Co-expression of vascular endothelial growth factor and thymidine phosphorylase in endometrial cancer.

OBJECTIVE: To examine expression of vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP) together with microvessel count in endometrial cancer, and to investigate the relationship with clinicopathological and biological factors. METHODS: VEGF expression, TP expression, the microvessel count (factor VIII-related antigen positive cells), bcl-2 expression, proliferating cell nuclear antigen (PCNA) index, and p53 expression were determined in 50 resected endometrial cancer specimens, using immunohistochemistry. The relationship between VEGF and TP expression and correlation between expression and microvessel count were also given attention. These 3 factors were analyzed with regard to clinicopathological factors, bcl-2 expression, PCNA index, and p53 expression. RESULTS: Staining status of VEGF and TP was identical in 37 (74%) of 50 tumors, the correlation being statistically significant (p < 0.01). Combined analysis of VEGF and TP status showed that tumors which were VEGF-positive and/or TP-positive had a significantly higher microvessel count than did tumors which were both VEGF-negative and TP-negative (p < 0.001 and p < 0.05, respectively). TP expression correlated with bcl-2 expression, and VEGF expression inversely correlated with the PCNA index. Although clinical stage (p < 0.01), PCNA index (p < 0.01), and p53 expression (p < 0.01) significantly correlated with disease-free survival, neither VEGF/TP expression nor microvessel count contributed to prognostic estimates. CONCLUSIONS: VEGF and TP may cooperatively promote angiogenesis in endometrial cancer, but these expressions may have limited additional prognostic value.

Adult↗
PubMed1999

[A multicenter early phase II study of high-dose chemotherapy with autologous peripheral blood stem cell transplantation for treatment of intermediate-grade non-Hodgkin's lymphoma. Japan Blood Cell Transplantation Study Group].

We conducted a multicenter early phase II study to evaluate the feasibility and therapeutic efficacy of high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation (auto-PBSCT) for the treatment of intermediate grade non-Hodgkin's lymphoma (IG-NHL). High-dose etoposide or cyclophosphamide followed by G-CSF was used for PBSC mobilization, and a sufficient number of CD34+ cells (> 1 x 10(6)/kg) were collected. Out of 81 enrolled patients, 50 received high-dose chemotherapy with auto-PBSCT; Hematologic recovery after transplantation was rapid. The incidence of grade III/IV toxicity (Bearman) was about 6%; treatment-related mortality was 6% (3/50). The Disease-free survival rate for the patients in complete remission who received high-dose chemotherapy with auto-PBSCT was better than that for the patients who were treated with conventional chemotherapy (57% vs 35%). These preliminary results indicated that high-dose chemotherapy with auto-PBSCT is feasible and effective. A prospective randomized phase III clinical trial will be required to assess the efficacy of high-dose chemotherapy with auto-PBSCT as a post-remission therapy for IG-NHL.

Adolescent↗
PubMed1998

Subcellular localization and protein-protein interaction regions of Ku proteins.

The Ku protein is a complex of Ku70 and Ku80 subunits and is capable of binding promoters in a sequence-specific manner, although it remains unclear whether Ku is involved in transcriptional regulation. We examined the subcellular localization and determined the interaction regions of Ku. Our results indicate that heterodimers of Ku70 and Ku80 are localized in the nucleus, and that the stretches from amino acid (aa) 378 to 482 of Ku70 and from aa 374 to 502 of Ku80 are necessary for heterodimerization. These interaction regions do not contain any previously recognized protein-protein interaction motifs. To determine whether Ku contains a potential transcriptional activation domain, we examined N- and C-terminal deletion mutants of Ku70 and Ku80 for their ability to activate transcription in the GAL4-based one-hybrid system. We found that the whole Ku protein had no transcriptional activity, although the N-terminal peptide fragment of Ku70 was capable of activating transcription of the HIS3 and lacZ reporter genes in yeast cells.

Antigens, Nuclear↗
PubMed1998

Telomerase activity in gastrointestinal stromal tumors.

BACKGROUND: Telomerase activity has been observed in 80-90% of carcinomas derived from various organs. However, to the authors' knowledge this report is the first assessment of telomerase activity in gastrointestinal stromal tumors (GISTs). METHODS: Telomerase activity was analyzed by the telomerase repeat amplification protocol assay in 29 tumors from 26 patients (23 primary tumors from 22 patients, 1 pair of primary and metastatic tumors from 1 patient, and 4 metastatic tumors from 3 patients). Phenotypes, tumor cell proliferation, and overexpression of p53 protein were evaluated immunohistochemically. RESULTS: Seven of 24 primary tumors (29%) and 5 of 5 metastatic tumors (100%) showed telomerase activity. Telomerase activity positive (+) GISTs were significantly larger (P < 0.05) and showed a significantly higher rate of proliferation than telomerase activity negative (-) tumors (P < 0.0001). All telomerase activity (+) GISTs were classified histologically as high risk tumors. Conversely, 15 of the 17 telomerase (-) GISTs were classified histologically as low risk tumors (P < 0.0001). With regard to p53 immunoreactivity, two and seven telomerase activity (+) tumors showed diffuse and sporadic positivity, respectively, whereas only five telomerase activity (-) tumors showed only focal or sporadic positivity. Telomerase activity was correlated significantly with poor prognosis (P < 0.05) in the patients in whom the primary GISTs were evaluated (n = 23). CONCLUSIONS: Telomerase activity may be a useful marker for evaluating the malignant potential of GIST. A distinct subgroup of GISTs is a target for therapy with a telomerase inhibitor.

Adult↗
PubMed1998

19-nor vitamin-D analogs: a new class of potent inhibitors of proliferation and inducers of differentiation of human myeloid leukemia cell lines.

We have studied the in vitro biological activities and mechanisms of action of 1,25-dihydroxyvitamin D3 (1,25D3) and nine potent 1,25D3 analogs on proliferation and differentiation of myeloid leukemia cell lines (HL-60, retinoic acid-resistant HL-60 [RA-res HL-60], NB4 and Kasumi-1). The common novel structural motiff for almost all the analogs included removal of C-19 (19-nor); each also had unsaturation of the side chain. All the compounds were potent; for example, the concentration of analogs producing a 50% clonal inhibition (ED50) ranged between 1 x 10(-9) to 4 x 10(-11) mol/L when using the HL-60 cell line. The most active compound [1, 25(OH)2-16,23E-diene-26-trifluoro-19-nor-cholecalciferol (Ro 25-9716)] had an ED50 of 4 x 10(-11) mol/L; in contrast, the 1,25D3 produced an ED50 of 10(-9) mol/L with the HL-60 target cells. Ro 25-9716 (10(-9) mol/L, 3 days) was a strong inducer of myeloid differentiation because it caused 92% of the HL-60 cells to express CD11b and 75% of these cells to reduce nitroblue tetrazolium (NBT). This compound (10(-8) mol/L, 4 days) also caused HL-60 cells to arrest in the G1 phase of the cell cycle (88% cells in G1 v 48% of the untreated control cells). The p27(kip-1), a cyclin-dependent kinase inhibitor which is important in blocking the cell cycle, was induced more quickly and potently by Ro 25-9716 (10(-7) mol/L, 0 to 5 days) than by 1,25D3, suggesting a possible mechanism by which these analogs inhibit proliferation of leukemic growth. The NB4 promyelocytic leukemia cells cultured with the Ro 25-9716 were also inhibited in their clonal proliferation (ED50, 5 x 10(-11) mol/L) and their expression of CD11b was enhanced (80% positive [10(-9) mol/L, 4 days] v 27% untreated NB4 cells). Moreover, the combination of Ro 25-9716 (10(-9) mol/L) and all-trans retinoic acid (ATRA, 10(-7) mol/L) induced 92% of the NB4 cells to reduce NBT, whereas only 26% of the cells became NBT positive after a similar exposure to the combination of 1,25D3 and ATRA. Surprisingly, Ro 25-9716 also inhibited the clonal growth of poorly differentiated leukemia cell lines (RA-res HL-60 [ED50, 4 x 10(-9) mol/L] and Kasumi-1 [ED50, 5 x 10(-10) mol/L]). For HL-60 cells, Ro 25-9716 markedly decreased the percent of the cells in S phase of the cell cycle and increased the expression of the cyclin-dependent kinase inhibitor, p27(kip-1). In summary, 19-nor vitamin D3 compounds strongly induced differentiation and inhibited clonal proliferation of various myeloid leukemia cell lines, suggesting a therapeutic niche for their use in myeloid leukemia.

Cell Cycle↗
PubMed1998

Crystallization and preliminary X-ray analysis of pig E3, lipoamide dehydrogenase.

Pig heart lipoamide dehydrogenase was crystallized by the hanging-drop vapor-diffusion method. X-ray diffraction patterns show that the hexagonal crystals have unit-cell dimensions of a = b = 359. 3, c = 140.5 A. The crystal structure has been preliminarily solved by the molecular-replacement method in the space group P6322. Three dimeric molecules have been found in the asymmetric unit, one of them located on the crystallographic twofold axis.

Animals↗
PubMed1998

19-nor-26,27-bishomo-vitamin D3 analogs: a unique class of potent inhibitors of proliferation of prostate, breast, and hematopoietic cancer cells.

Vitamin D3 [1,25-dihydroxyvitamin-D3 (1,25(OH)2D3)] modulates the proliferation and differentiation of many cell types. Analogs of 1,25(OH)2D3 that have greater potency may become adjuvant therapy for breast and prostate cancers, myelodysplastic syndrome, acute myelogenous leukemia in remission and other cell types, especially in the setting of low disease burden. A new class of analogs of 1,25(OH)2D3 has been synthesized that has a novel 19-nor motif, as well as incorporating many structural elements previously shown to increase potency. These analogs were examined for their effects on prostate cancer cell lines (PC-3, LNCaP, and DU 145), a human breast cell line (MCF-7), and an acute myeloid leukemia cell line (HL-60). Dose-response clonogenic studies showed that each of these analogs had more potent antiproliferative activities against the cancer cells than 1,25(OH)2D3, and 1,25-(OH)2-16,23Z-diene-26,27-bishomo-19-nor-D3 (Ro 27-2014) was the most potent analog [10-fold increased activity compared to 1,25(OH)2D3]. Further studies were performed using Ro 27-2014. Pulse-exposure studies showed that a 5-day pulse-exposure to Ro 27-2014 (10(-7) M) in liquid culture was adequate to achieve a 50% inhibition of MCF-7 clonal growth in soft agar in the absence of the analog, suggesting that the growth inhibition mediated by the analog was irreversible. Cell cycle analyses using MCF-7 cells showed that Ro 27-2014 (10(-7) M for 4 days) induced a significant increase in the number of cells in G0-G1 (72.8+/-8.9% versus 49.9+/-3.5% in control cells), with a concomitant decrease in the percent of cells in S phase (13.1+/-6.2% versus 35.8+/-3.5% in control cells). The chief toxicity of vitamin D3 compounds is hypercalcemia, and therefore, we examined calcemic activity of Ro 27-2014 in mice and found it not to induce hypercalcemia at doses of 0.05 microg i.p. three times per week. In contrast, the same dose of a 19-nor vitamin D3 compound with 6 fluorines on the side chain (1,25-(OH)2-16-ene-23-yne-26,27-F6-19-nor-D3), although also having potent anticancer activity, caused severe hypercalcemia (18 mg/dl). In summary, 19-nor vitamin D3 compounds with desaturation and lengthening of their side chains result in a series of compounds with a good therapeutic index, having potent anticancer activity and low toxicity.

Animals↗
PubMed1998

Myelodysplastic syndrome after regression of transient abnormal myelopoiesis in a Down syndrome infant: different clonal origin?

A boy with Down syndrome who developed myelodysplastic syndrome after regression of transient abnormal myelopoiesis (TAM) is described. His blast cells in TAM had other chromosome abnormalities in addition to trisomy 21;50,XY,+21c,+12,+14,+21. Serial chromosome analysis in follow-up showed abnormal clones involving monosomy 7. Myelodysplastic syndrome was diagnosed. Because two clones had different karyotypes, they might have derived from different clones.

Chromosome Aberrations↗
PubMed1998

Frequent loss of heterozygosity on the long arm of chromosome 6: identification of two distinct regions of deletion in childhood acute lymphoblastic leukemia.

Cytogenetic analysis of childhood acute lymphoblastic leukemia (ALL) identified nonrandom chromosomal abnormalities of the long arm of chromosome 6. Most of the alterations are deletions that are thought to be indicative of the presence of a tumor suppressor gene that is mutated on the remaining allele. These observations led us to consider whether 6q loss may contribute to the pathogenesis of childhood ALL. To define further a region containing this gene, we analyzed the loss of heterozygosity (LOH) of chromosome 6 in 113 primary ALL samples with matched normal DNA using 34 highly informative microsatellite markers. LOH was found in 17 (15%) samples at one or more of the loci, and partial or interstitial deletions of 6q were detected in 11 of these tumors. On the basis of these results, we performed a detailed deletional map and identified two distinct regions of deletion. The first region is flanked by D6S283 and D6S302 loci at 6q21-22. The second region is flanked by D6S275 and D6S283 loci at 6q21. Clinical analysis determined that LOH of 6q was demonstrated both in precursor-B cell ALLs (15 of 93; 16%) and in T cell ALLs (2 of 19; 11%). In addition, 19 patients have been studied at diagnosis and relapse; 18 showed the same 6q21-22 structural abnormality at relapse (normal, 16 patients; LOH, 2 patients) as their initial presentation, suggesting, albeit with a small patient sample size, that 6q21-22 deletions may be an initial event in leukemogenesis and may occur less frequently during the progression of childhood ALL. These data suggest the presence of putative tumor suppressor genes on chromosome arm 6q that are important in the development of both T and precursor-B childhood ALLs. Our map provides important information toward cloning putative ALL tumor suppressor genes.

Child↗
PubMed1998

High frequency of fibroblast growth factor (FGF) 8 expression in clinical prostate cancers and breast tissues, immunohistochemically demonstrated by a newly established neutralizing monoclonal antibody against FGF 8.

Fibroblast growth factor (FGF) 8, also known as androgen-induced growth factor, was originally isolated from an androgen-dependent mouse mammary Shionogi carcinoma SC-3 cell line, in which it was shown to have androgen-regulated properties. We previously demonstrated that Fgf 8 transcripts were detected in several human prostate and breast cancer cell lines and that recombinant FGF 8 was mitogenic to an androgen-sensitive prostate cancer LNCaP cell line. In this study, to characterize the roles of FGF 8 in clinical hormone-responsive cancers, we established a monoclonal antibody against FGF 8. In Western blots, this antibody specifically interacted with a FGF 8b isoform that was identical between mouse and human but was not identical to other murine 8a and 8c isoforms. In a cell growth assay using SC-3 cells, the newly established anti-FGF 8 antibody blocked androgen- and FGF 8-stimulated growth but not basic FGF-stimulated growth. Immunohistochemical analyses by use of the established anti-FGF 8 antibody demonstrated that FGF 8 was frequently expressed in human prostate cancers, appearing in 40 of 43 cases (93%), whereas both prostatic hyperplasia specimens and normal prostate tissues included in biopsy specimens were negative for FGF 8 expression. On the other hand, FGF 8 was detected in normal ductal and lobular epithelial cells in breast tissues. FGF 8 was also frequently expressed in various breast diseases, including fibroadenomas (5 of 5 cases, 100%), intraductal papillomas (3 of 3 cases, 100%), ductal hyperplasias (3 of 6 cases, 50%), and breast cancers (8 of 12 cases, 67%). Androgen receptors were also immunohistochemically detected in FGF 8-positive prostate cancers (40 of 40 cases, 100%) and FGF 8-positive breast diseases (17 of 19 cases, 89%). These findings strongly suggest that FGF 8 is involved in hormone-related tumorigenesis of the prostate and breast.

Animals↗
PubMed1998

Ti/Al multilayer zone plate and Bragg-Fresnel lens.

By using a helicon plasma sputtering technique, a one-dimensional Ti/Al multilayer zone plate with an outermost layer width of 76 nm has been successfully fabricated. A Bragg-Fresnel lens has been made by combining this zone plate with a Ge(422) crystal. Comparison of the Ti/Al multilayer zone plate with the Ag/Al zone plate is discussed in terms of focusing efficiency.

Journal Article↗
PubMed1998

The operation of a superconducting wiggler at TERAS.

A superconducting wiggler has been successfully installed at the ETL 800 MeV electron storage ring facility (TERAS). The operation of the wiggler at magnetic field strengths of 5 T with electron beam energy of 750 MeV has been accomplished. The wiggler has been designed and constructed to produce synchrotron radiation with critical photon energy around 3 keV for scientific, industrial and medical applications. We report here experiments that demonstrate the possibility of stable operation of a superconducting wiggler in a small storage ring.

Journal Article↗