Biomedical subjects

Kouichi Wada

Publications and source records attributed to Kouichi Wada.

9 recordsLinked to original sources

PubMed2005

Inhibition of glioma cell proliferation by neural stem cell factor.

Neural stem cells (NSC) have unique differentiation-, proliferation-, and motility properties. To investigate whether they secrete factors that interfere with the proliferation of glioma cells, we grew glioma cells in conditioned medium (CM) obtained from cultures of neurospheres including neural stem / progenitor cells (NSPC) isolated from embryonic (E14)- or adult mouse brain or fetal human brain. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and BrdU-labeling assays showed that CM from NSPC (NSPC/CM) contained factor(s) that inhibited the proliferation of glioma cells by 28-87%. Filter-fractionation of NSPC/CM revealed that the 50,000-100,000 nominal molecular weight limit (NMWL) fraction contained the inhibitory activity. On the basis of these observations we transplanted 203G glioma cells and/or NSPC into the intrathecal space of the cisterna magna of mice to investigate whether NSPC interfere with the proliferation of glioma cells in vivo. Mice transplanted with both 203G and NSPC survived significantly longer than did mice transplanted only with 203G. We concluded that NSPC secrete factor(s) that may control glioma cell proliferation.

Animals↗

PubMed2005

Ganglioside GM3 inhibits proliferation and invasion of glioma.

GM3, the simplest ganglioside, modulates cell adhesion, proliferation and differentiation in the central nervous system and exogenously added GM3 regulates cell-cell and cell-extracellular matrix adhesion and induces apoptosis. To assess the anti-tumor action of exogenous GM3, we examined its effect on the proliferation and invasion of glioma cells. Its inhibitory effect on cell proliferation was demonstrated in vitro by 3-(4,5-dimethyl-2-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay and in vitro in rats with meningeal gliomatosis whose survival was significantly prolonged by the intrathecal injection of GM3. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay revealed that GM3 induced glioma cell apoptosis in vitro and in vitro. In rat brain slice cultures, GM3 suppressed the invasion of glioma cells; this effect manifested earlier than the inhibition of cell proliferation and before apoptosis induction. Our results suggest exogenous GM3 as a potential therapeutic agent in patients with glioma requiring adjuvant therapy.

Animals↗

PubMed2005

Immunohistochemical detection of female sex hormone receptors in craniopharyngiomas: correlation with clinical and histologic features.

BACKGROUND: Although craniopharyngiomas have a histologically benign nature, their treatment can be difficult. The correlation among clinical, proliferative, and immunohistologic features of female sex hormone receptors was determined in craniopharyngiomas to analyze whether they influence the growth of the tumor. METHODS: The study subjects were 43 patients with previously untreated craniopharyngioma who underwent surgery at our department over the past 15 years. Serial tissue sections were immunostained with the antibodies against estrogen receptor (ER), progesterone receptor (PR), and Ki-67. RESULTS: The Ki-67 labeling index was significantly higher in patients with regrowth (7.8%) than without regrowth (3.9%). ER and PR were detected in 9 of 30 (30%) craniopharyngiomas, and the incidence of postoperative tumor regrowth was significantly higher in patients negative for ER and PR (29%) than in those positive for both receptors (11%). CONCLUSIONS: A high Ki-67 labeling index suggests a high possibility of tumor regrowth, and the presence of ER and PR is suggestive of a high tissue differentiating potential. ER and PR assay may be useful for determining the indication for additional radiation therapy in craniopharyngioma patients treated by incomplete resection.

Adolescent↗

PubMed2005

Chromosomal and genetic abnormalities in benign and malignant meningiomas using DNA microarray.

BACKGROUND: Meningioma is the commonest brain tumor and many genetic abnormalities, such as the loss of chromosome 22q and the mutation of NF2, have been reported. METHODS: These classical abnormalities were detected using Southern blot, PCR, fluorescence in situ hybridization and comparative genomic hybridization, but these methods examine only very limited regions or limited mapping resolution of the tumor genome. In this study, we used DNA microarray assay, which detects numerous genetic abnormalities simultaneously and analyses a global assessment of molecular events in meningioma cells. We studied 31 meningiomas by GenoSensor Array 300 in order to detect the chromosomal aberrations and genetic abnormalities in the whole genome. RESULTS: This study demonstrated not only classical chromosomal aberration, such as loss of chromosome 22q in 19 meningiomas (61.3%), but also new genetic characteristics of meningiomas, such as amplification of MSH2 in 16 meningiomas (51.6%), deletion of GSCL in 13 meningiomas (41.9%) and deletion of HIRA in seven meningiomas (22.6%). CONCLUSIONS: These results suggest that DNA microarray assay is useful in research for the genetic characters of meningiomas and understanding tumorigenesis.

Adolescent↗

PubMed2004

Synthesis and pharmacological evaluation of piperidinoalkanoyl-1,2,3,4-tetrahydroisoquinoline derivatives as novel specific bradycardic agents.

A series of piperidinoalkanoyl-1,2,3,4-tetrahydroisoquinoline derivatives were synthesized, and their bradycardic activities were investigated in the isolated right atria of guinea pigs and in conscious rats. These efforts identified the achiral compound 2f, which exhibited potent and long-lasting bradycardic activity with minimal effects on mean blood pressure in conscious rats.

Animals↗

PubMed2004

Synthesis and pharmacological evaluation of N-acyl-1,2,3,4-tetrahydroisoquinoline derivatives as novel specific bradycardic agents.

A series of N-acyl-1,2,3,4-tetrahydroisoquinoline derivatives were synthesized and evaluated for their bradycardic activities in isolated guinea pig right atria and in urethane-anesthetized rats. These efforts resulted in identification of the compound 8a, which exhibits potent bradycardic activity with minimal influence on mean blood pressure in urethane-anesthetized rats. Oral administration of compound 8a to conscious rats revealed increased potency and prolonged duration of action when compared to Zatebradine.

Administration, Oral↗

PubMed2004

Genetic analysis of human glioblastomas using a genomic microarray system.

Genomic microarray systems can simultaneously provide substantial genetic and chromosomal information in a relatively short time. We have analyzed genomic DNA from frozen sections of 30 cases of primary glioblastomas by GenoSensor Array 300 in order to characterize gene amplifications, gene deletions, and chromosomal information in the whole genome. Genes that were frequently amplified included RFC2/CYLN2 (63.3%), EGFR (53.3%), IL6 (53.3%), ABCB1 (MDR1) (36.7%), and PDGFRA (26.7%). Genes that were frequently deleted included (56.7%), FGFR2 (66.7%), MTAP (60.0%), DMBT1 CDKN2A (p16)/MTAP (50.0%), PIK3CA (43.3%), and EGR2 (43.3%), but deletion of RB1 or TP53 was rarely detected. Chromosomal gains were observed frequently for 7q (33.3%), 7p (20.0%), and 17q (13.3%). Loss of the 10q was frequently detected in 13 of 30 cases (46.7%). Loss of the entire chromosome 10 was seen in 9 of 30 cases (30.0%), and was often accompanied by EGFR amplification (7 cases, 77.8%). The GenoSensor Array 300 proved to be useful for identification of genome-wide molecular changes in glioblastomas. The obtained microarray profile can also yield valuable insight into the molecular events underlying carcinogenesis of brain tumors and may provide clues about clinical correlations, including response to treatment.

Adult↗

PubMed2004

Chromosomal and genetic aberrations differ with meningioma subtype.

Meningioma is one of the most common brain tumors, and a variety of genetic abnormalities have been detected by the Southern blotting, polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), and comparative genomic hybridization (CGH) methods. However, these methods detect only a very limited portion of the tumor genome or have a limited mapping resolution. In this study, we used DNA microarray assay, which detects numerous genetic abnormalities and analyzes a global assessment of molecular events in tumor cells. We analyzed genomic DNA from 26 patients with benign meningiomas by GenoSensor Array 300 in order to characterize gene amplifications, gene deletions, and chromosomal information in the whole genome. Loss of chromosome 22q was found most frequently. This chromosomal aberration was detected in 14 meningiomas (53.8%), particularly in transitional and fibrous meningiomas. In meningothelial meningiomas, amplification of INS and TCL1A was detected more frequently than in other meningioma subtypes. DNA microarray assay revealed new genetic differences among the meningioma subtypes, thus indicating that this novel technique is useful for understanding tumor genesis and for the diagnosis of meningioma subtype.

Adolescent↗

PubMed2002

Postoperative modified stereotactic radiotherapy using a micro-multileaf collimator in patients with malignant glioma.

To achieve local control of malignant glioma, we designed a postoperative stereotactic radiotherapy using a micro-multileaf collimator (micro-MLC). The purpose of this study was to clarify the feasibility of this treatment. The treatment was performed in six patients who met the following eligibility criteria: (1) supratentorial tumor, (2) residual tumor volume < or = 40 cm3, and (3) Karnofsky performance status > or = 70. The three planning target volumes (PTVs), which consisted of restricted PTV (RPTV), intermediate PTV (IPTV), and extended PTV (EPTV), defined as the residual tumor plus a 1 cm, 2 cm, and 3 cm margins, respectively, and total dose delivery of 60-68 Gy, 52-60 Gy, and 44-52 Gy to the isocenters of RPTV, IPTV, and EPTV, respectively, in 4 Gy per fraction at five fractions per week, were established. The beam arrangement and the conformal blockade with a micro-MLC for the optimal treatment plan were designed. The treatment plans showed the high dose conformation to EPTV, the appropriate dose gradients in the three PTVs with the high dose homogeneity to RPTV, and the tolerated dose to critical structures. Following the plans, treatment was performed. The clinical findings more than 12 months after the treatment supported its possible use. We conclude that this treatment is feasible at least in selected patients.

Adult↗