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Yuichiro Tanaka

Publications and source records attributed to Yuichiro Tanaka.

At least 73 records · Page 4Linked to original sources
PubMed2003

Quercetin regulates growth of Ishikawa cells through the suppression of EGF and cyclin D1.

Quercetin and other polyphenols have anti-carcinogenic and anti-tumorigenic activity in various organs, however, studies of this activity are lacking in endometrial cancer. We hypothesize that quercetin has anti-proliferative activity and the mechanisms of quercetin action may be through modulation of cell cycle and cell growth regulatory genes. To test this hypothesis, we treated endometrial cancer cells (Ishikawa cell line) with quercetin, and cell proliferation, expression of growth signal genes (EGF, VEGF, and TGF-alpha), cell cycle genes (p53, p21, p73, and cyclin D1), and apoptosis-related genes (bcl-2 and bax) were analyzed. Results of these experiments demonstrate that after a 7-day exposure to 1, 10 and 100 micro M of quercetin, growth of Ishikawa cells was inhibited by 3, 51 and 87%, respectively. The gene and protein expression data suggest that quercetin treatment (100 micro M) significantly decreased EGF and cyclin D1, whereas VEGF was up-regulated in Ishiwaka cell lines. Other genes such as TGF-alpha, p53, p21, p73, bcl-2 and bax were not significantly changed with quercetin treatment in Ishiwaka cell lines. The present study suggests that quercetin can suppress proliferation of Ishikawa cells through down-regulation of EGF and cyclin D1.

Cyclin D1↗
PubMed2003

Resveratrol suppresses growth of Ishikawa cells through down-regulation of EGF.

Resveratrol and other polyphenols have anti-carcinogenic and anti-tumorigenic activities in various carcinomas. However, such studies are limited in endometrial cancer. We hypothesize that resveratrol suppresses cancer growth through modulation of cell cycle and cell growth regulatory genes. To test this hypothesis, we treated endometrial cancer cells (Ishikawa cell line) with resveratrol (1, 10, 50 and 100 micro M) for 1, 3, 5 and 7 days, and analyzed for growth signal genes (EGF and VEGF), cell cycle regulatory genes (p53 and p21), and apoptosis-related genes (bcl-2 and bax). Results of these experiments demonstrate that after resveratrol treatment, the growth of Ishikawa cells was inhibited in a dose dependent manner. The gene and protein expression data suggest that resveratrol treatment significantly decreased EGF, whereas VEGF was up-regulated in Ishiwaka cell lines. Interestingly, protein expressions of p21 and Bax were decreased, even though their mRNA expressions did not show significant changes. The present study suggests that resveratrol can suppress proliferation of Ishikawa cells through down-regulation of EGF.

Antineoplastic Agents, Phytogenic↗
PubMed2002

Novel synthesis of methylenecyclobutanols and 4-methylenetetrahydrofurans from gamma-oxide ylides.

The reaction of delta-halo-gamma-oxide ylide, prepared from methylenetriphenylphosphorane and epichlorohydrin, with aldehydes afforded alkylidenecyclobutanols in moderate yields. The reaction initially proceeded through internal nucleophilic attack on delta-carbon of this ylide. Another novel approach toward the synthesis of 4-methylenetetrahydrofurans was achieved by the reaction of gamma-oxide ylides with paraformaldehyde.

Journal Article↗
PubMed2002

Polymorphisms of estrogen receptor alpha gene in endometrial cancer.

It is hypothesized that polymorphisms of estrogen receptor-alpha (ERalpha) gene are involved in endometrial cancer. To test this hypothesis, the genotype distributions of six different loci (codon 10 T-->C, codon 87 G-->C, codon 243 C-->T, codon 325 C-->G, codon 594 G-->A, and intron 1 C-->G) of the ERalpha gene were investigated and their association with endometrial cancer was determined. The DNA from 113 cases of human endometrial cancer was analyzed by sequence-specific polymerase chain reaction. The relative risk of variant genotype was calculated by comparison with 200 healthy controls. The frequency of variant genotype on codon 10 was significantly lower in endometrial cancer patients as compared to controls. Nine of 113 endometrial cancer patients (8.0%) showed genotype 10C/C compared to 27 of 200 healthy controls (13.5%). The relative risk of genotype 10C/C was calculated as 0.44, compared to wild-type. Forty-five of 113 endometrial cancer patients (39.8%) showed genotype T/C on codon 10 compared to 111 of 200 healthy controls (55.5%). The relative risk of genotype 10T/C was calculated as 0.67, compared to wild-type. The polymorphism on codon 87 was not detected both in endometrial cancer patients and in healthy control. Other loci, intron 1, and codons 243, 325, and 594, did not show a correlation with endometrial cancer. The frequency of alleles on codon 10 was also significantly lower in endometrial cancer patients as compared to controls. Sixty-three of 226 alleles (27.9%) of endometrial cancer patients showed allele C compared to 165 of 400 (41.2%) of healthy controls. The relative risk of allele 10C was calculated as 0.67, compared to wild-type. Other loci, intron 1, and codons 243, 325, and 594, did not show a difference between cancer patients and controls. All genotype and allelic distributions were in accordance with the Hardy-Weinberg equilibrium. The present study demonstrates for the first time a protective effect of 10C allele against endometrial cancer. Thus, inherited alterations in ERalpha may be associated with changes in estrogen metabolism and thereby may possibly explain inter-individual differences in disease incidences of endometrial cancer.

Adult↗
PubMed2002

Single nucleotide polymorphisms of estrogen receptor alpha in human renal cell carcinoma.

Estrogens and their receptors (ERs) have been shown to play a role in various cancers. We hypothesize that polymorphisms and genotypic changes of the ERalpha gene are involved in renal cell carcinoma. To test this hypothesis, DNA samples from 113 cases of human renal cell cancer were analyzed by sequence-specific polymerase chain reaction to determine the genotypic frequency of six different polymorphic loci on ERalpha gene (codon 10 T-->C, codon 87 G-->C, codon 243 C-->T, codon 325 C-->G, codon 594 G-->A, and intron 1 C-->T). The relative risk of variant genotype was calculated by comparison with 200 healthy controls. The results of this study demonstrate that the distribution of genotypes on codon 10 differs between renal cancer patients and healthy normal controls (p<0.05). The relative risk of the genotype 10C/C was calculated as 2.51. No differences in genotypes were observed at all other loci. We also analyzed DNA from pairs of cancerous and normal tissues from 96 cases of human renal cell cancer to characterize genotypic changes at these loci. Genotypic changes were detected in nine cancer samples on exon 1 (codons 10 and 87) of ERalpha, although none were detected at other regions. The present study demonstrates for the first time that codon 10 polymorphism on exon 1 of ERalpha may be involved in renal cancer risk.

Carcinoma, Renal Cell↗
PubMed2002

Polymorphisms of the CYP1B1 gene have higher risk for prostate cancer.

Various carcinogenic factors including estrogen metabolites play a role in malignant transformation. These metabolites are formed in part, as a result of the hydroxylation activity of cytochrome P450 (CYP) 1B1. Variant forms of this enzyme have been shown to enhance its activity, and thus, we hypothesize that single nucleotide polymorphisms of the CYP1B1 gene can be a risk factor for prostate cancer. To test this hypothesis, the genetic distribution of six different CYP1B1 polymorphisms at intron 1 (C-->T), codon 48 (C-->G), codon 119 (G-->T), codon 432 (C-->G), codon 449 (C-->T), and codon 453 (A-->G) was analyzed in 117 prostate cancer samples and 200 healthy normal subjects from a Japanese population. Results of these experiments demonstrate that the genotype at codon 119 is significantly different between prostate cancer patients and controls (P<0.001). The odds ratio of genotype T/T compared to G/G (reference) was calculated as 4.02 with a 95% confidence interval of 1.73-9.38. All other codons, except 453, showed polymorphisms but were not significantly different between cancer patients and controls. No association was found between stage and grade of cancer with any of the polymorphic sites. This is the first report that demonstrates the polymorphism at codon 119 of CYP1B1 to be associated with prostatic carcinogenesis. These results are important in understanding the role of CYP1B1 polymorphisms in the pathogenesis of prostate cancer.

Alleles↗
PubMed2002

Transforming growth factor-beta(s) and their receptors in aging rat prostate.

We hypothesize that rat fetal urogenital sinus mesenchyme (UGM) can induce prostatic growth of growth quiescent adult rat prostate through modulations of TGFbetas and their receptors. To test this hypothesis, prostatic ducts from aging rat prostate (4, 12, 17, 22, and 27 months) were combined with fetal rat UGM and grafted under renal capsule of athymic nude mice. At 1, 3, and 5 months the tissue recombinants were harvested from renal capsule and analyzed for their growth. The gene and protein expression of TGFbeta1, 2, 3 and their receptors, TbetaR-I and TbetaR-II, were analyzed by RT-PCR and immunohistochemistry, respectively. The results of these experiments demonstrate that prostate ducts when combined with rat UGM formed larger grafts as compared to control (prostatic ducts without UGM). The older rat prostate recombinants (17, 22, and 27 months) formed larger grafts (159 mg/graft) as compared to younger rat prostate (4 and 12 months) grafts (51 mg/graft). The mRNA and protein expression for TbetaR-I and TbetaR-II in 22 and 27 months rat prostate tissue recombinants were significantly lower than 4, 12, and 17 month tissue recombinants. However, mRNA expression for TGFbeta1, TGFbeta2, and TGFbeta3 did not change with aging rat tissue recombinants. The protein expression for TGFbeta1 was significantly up-regulated whereas TGFbeta2 and TGFbeta3 were down-regulated with aging prostate tissue recombinants. The present study demonstrates for the first time that rat fetal UGM differentially induces growth of aging rat prostate in a tissue recombinant model. The mechanisms of induction may be through up-regulation of TGFbeta1 and down-regulation of TGFbeta2, and TGFbeta3. However, the action of TGFbetas may be through TbetaR-I and TbetaR-II independent pathways since these receptors were lacking or low in older rat prostate tissue recombinants. These findings are important in understanding the mechanisms of UGM mediated prostatic growth.

Activin Receptors, Type I↗
PubMed2002

Effects of aging on growth factors gene and protein expression in the dorsal and ventral lobes of rat prostate.

We hypothesize that various growth factors and their receptors gene and protein are modulated in dorsal and ventral lobes of aging prostate. To test this hypothesis, TGFbeta1, TGFbeta2 TGFbeta3, TGFbetaR-I, TGFbetaR-II, TGFalpha, EGF, EGFR, KGF and KGFR gene and protein expression were analyzed in dorsal and ventral lobes of aging rat prostates (1, 3, 6, 9, 12, 18, 24, and 28/30 months). KGF gene expression was very weak or absent in 1, 3, and 6 month old rat dorsal and ventral lobes of prostate whereas it re-expressed in 9, 12, 18, 24 and 30 month old rat prostate. All growth factors and their receptors expect KGF and EGFR were mainly localized in epithelium of ventral and dorsal lobes of aging rat prostates. EGF, TGFalpha, TGFbeta1, and TGFbetaR-I protein expression was lacking in stroma of dorsal and ventral lobes of 1, 3, 6, 9, 12/18 months old rat prostates. However, EGF, TGFbeta1 and TGFbetaR-I proteins re-expressed in stroma of 24 and 28 months old rat prostates. KGF protein expression was lacking in epithelium of dorsal and ventral lobes of all aging rat prostates. This is the first report to demonstrate differential gene and protein expression of growth factors in dorsal and ventral lobes is associated with aging rat prostate, suggesting their role in pathogenesis of prostatic diseases with aging.

Aging↗
PubMed2002

Methylation and inactivation of estrogen, progesterone, and androgen receptors in prostate cancer.

BACKGROUND: Prostate cancer development is initially steroid hormone dependent. Estrogen receptors (ERs), androgen receptors (ARs), and progesterone receptors (PRs) have been identified in normal and cancerous prostate tissues. We investigated whether the promoter regions of these steroid receptor genes are methylated and inactivated in prostate cancer cells and tissues. METHODS: The expression and promoter methylation status of three ERalpha isoforms (ERalpha-A, ERalpha-B, and ERalpha-C), ERbeta, two PR isoforms (PR-A and PR-B), and AR were investigated in five prostate cancer cell lines (ND1, DU145, PC3, LNCaP, and DUPro) and in pairs of normal and cancerous prostate tissues from 38 patients with prostate cancer. Methylation-specific polymerase chain reaction, reverse transcription--polymerase chain reaction, and 5' rapid amplification of complementary DNA ends were used. All statistical tests were two-sided. RESULTS: ERalpha-C was expressed in all cell lines, but ERalpha-A and ERalpha-B were not expressed in any cell line. ERalpha-A and ERalpha-B promoters were methylated, but ERalpha-C was unmethylated. Promoters for ERbeta, AR, PR-A, and PR-B were methylated and thus inactivated in some cell lines but not in others. Treating cells with the demethylating reagent 5-aza-2'-deoxycytidine restored expression of all steroid receptor genes with previously methylated promoters. All 38 pairs of cancer and normal tissues had unmethylated ERalpha-C promoters. Thirty-six (95%) of 38 cancers had methylated ERalpha-A, 35 (92%) of 38 cancers had methylated ERalpha-B, but all normal tissues had unmethylated ERalpha-A and ERalpha-B (both P<.001). ERbeta was methylated in 30 (79%) of 38 cancers but unmethylated in all normal tissues. AR was methylated in three (8%) of 38 cancers but unmethylated in all normal tissues. PR-A and PR-B were unmethylated in all tissues. CONCLUSION: Certain steroid receptor genes appear to be inactivated by CpG methylation in prostate cancer tissue and cell lines.

DNA Methylation↗
PubMed2002

Loss of anti-apoptotic genes in aging rat crura.

PURPOSE: Erectile dysfunction is a common problem in aging men. The molecular mechanisms associated with aging erectile dysfunction are not completely understood. We hypothesized that apoptosis is a downstream event in erectile dysfunction, and pro-apoptotic (Bak and Bax) and anti-apoptotic (Bcl-2 and Bcl-x) factors are involved in the etiology of aging erectile dysfunction. To test this hypothesis intracavernous pressure in aging rats was measured to assess erectile function. Gene and protein expression of pro-apoptotic and anti-apoptotic factors was then analyzed in aging rat crura to assess its role in aging erectile dysfunction. MATERIALS AND METHODS: A total of 25 male Sprague-Dawley rats divided into 5 groups of 5 each based on age (6, 12, 18, 24 and 28 months old, respectively) were used in functional and apoptotic studies. In addition, 5, 3-month-old male Sprague-Dawley rats were used in the apoptotic study. The rats were anesthetized with pentobarbital. Erectile function was assessed by measuring intracavernous pressure after electrostimulation of the cavernous nerves. After completion of the functional study the penile crura were immediately harvested for histochemical and molecular studies. Gene expression of pro-apoptotic (Bak and Bax) and anti-apoptotic (Bcl-2 and Bcl-x) factors were then analyzed by reverse transcription-polymerase chain reaction. Protein expressions of these apoptotic factors were also analyzed by immunohistochemistry using specific antibodies. RESULTS: Mean intracavernous pressure plus or minus SD in 18, 24 and 28-month-old rats was significantly lower than in 6-month-old rats (101.6 +/- 24.8, 77.7 +/- 24.5 and 45.7 +/- 7.3 versus 136.7 +/- 11.4 cm. water, respectively; p <0.05). The reduction in intracavernous pressure was an age dependent phenomenon. Gene and protein expression of the pro-apoptotic genes Bak and Bax was detected in the crura of all age groups but there was no significant difference in young and old rat crura. The anti-apoptotic Bcl-2 and Bcl-x genes were expressed in 3, 6 and 12-month-old crura, whereas this expression was lost at 18, 24 and 28 months. Anti-apoptotic Bcl-2 and Bcl-x proteins were also expressed in young rat crura, whereas this expression was lost in old rat crura. CONCLUSIONS: The decline in intracavernous pressure correlated significantly with a loss of anti-apoptotic genes in aging rat crura. To our knowledge this is the first report to show the loss of anti-apoptotic factors in aging rat crura and suggest their role in the pathogenesis of aging erectile dysfunction.

Aging↗
PubMed2002

Chronic subdural hematoma after transsphenoidal surgery.

Chronic subdural haematoma has not been reported as a complication of transsphenoidal surgery. We present a case of pituitary adenoma which was gross-totally removed by transsphenoidal surgery with the enlarged sellar opening. Postoperative serial imaging showed massive air accumulation in both frontal subdural spaces followed by subdural fluid collection and subsequent chronic subdural haematomas 2 months later. We conclude that close follow up imaging study is required to avoid overlooking chronic subdural haematoma when massive air is introduced into the subdural space by the transsphenoidal surgery.

Adenoma↗
PubMed2002

Aneurysm originating from the fenestration of the posterior cerebral artery: case report.

OBJECTIVE AND IMPORTANCE: A rare case of an aneurysm arising at the fenestration of the P2 segment of the posterior cerebral artery is reported. CLINICAL PRESENTATION: A 37-year-old man presented with severe headache and disturbance of consciousness. Computed tomographic scanning showed diffuse subarachnoid hemorrhage. Cerebral angiography revealed an aneurysm at the fenestration of the P2 segment of the right posterior cerebral artery. The aneurysm was located at the middle portion of the lower trunk of the fenestration. An unruptured arteriovenous malformation was incidentally found in the right thalamus. INTERVENTION: A right frontotemporal craniotomy with orbitozygomatic osteotomy was made, and the aneurysm was successfully clipped. One year after the operation, gamma knife surgery was performed for the right thalamic arteriovenous malformation. CONCLUSION: This is the first reported case of an aneurysm originating from the middle portion of a fenestrated posterior cerebral artery.

Adult↗
PubMed2002

Disturbed spatial learning of rats after intraventricular administration of transforming growth factor-beta 1.

Patients with subarachnoid hemorrhage (SAH) who later suffer hydrocephalus show persistently high levels of transforming growth factor-beta 1 (TGF-beta 1) in the cerebrospinal fluid after the onset of SAH. Recombinant TGF-beta 1 induces hydrocephalus in mice. This study examined the spatial learning ability of rats after intraventricular administration of TGF-beta 1. Thirteen-week-old Wistar rats were treated with 0.8 or 8.0 micrograms of human recombinant TGF-beta 1 by direct injection or via osmotic pump. Three months later, their spatial learning ability was evaluated with a Morris water maze. Ventricular size, ultrastructural features, and sodium-potassium-adenosine triphosphatase (Na+, K(+)-ATPase) activity of the subarachnoid space were examined. All three TGF-beta 1-treated groups clearly exhibited impaired spatial learning ability, but they did not exhibit ventricular dilation. Histological examination revealed subarachnoid fibrosis and deactivation of Na+, K(+)-ATPase in the arachnoid cells. These findings are similar to those of our previous experiments involving injection of TGF-beta 1 in mice. The present and previous studies suggest that subarachnoid fibrosis is an important factor in the disturbance of the spatial learning ability of rats, whereas ventricular size is less important.

Animals↗
PubMed2002

Radiometric analysis of paraclinoid carotid artery aneurysms.

OBJECT: Classification of paraclinoid carotid artery (CA) aneurysms based on their associated branching arteries has been confusing because superior hypophyseal arteries (SHAs) are too fine to appear opacified on cerebral angiograms. The authors performed a retrospective radiometric analysis of surgically treated paraclinoid aneurysms to elucidate their angiographic and anatomical characteristics. METHODS: A retrospective analysis was made of 85 intradural paraclinoid aneurysms in which the presence or absence of branching arteries had been determined at the time of surgical clipping. The lesions were classified as supraclinoid, clinoid, and infraclinoid aneurysms based on their relation to the anterior clinoid process on lateral angiograms of the CA. The direction of the aneurysms were measured according to angles formed between the medial portion of the horizontal line crossing the aneurysm sac and the center of the aneurysm neck on anteroposterior angiograms. Branching arteries were associated with 68 aneurysms, of which 28 were ophthalmic artery (OphA) lesions (32.9%) and 40 were SHA ones (47.1%); associated branching arteries were absent in 17 aneurysms (20%). Twenty-five aneurysms (29.4%) were located at the supraclinoidal level, 46 (54.1%) at the clinoidal, and 14 (16.5%) at the infraclinoidal. The majority of aneurysms identified at the supraclinoidal level were OphA lesions (44%) or those unassociated with branching arteries (48%), with mean directions of 57 degrees or 67 degrees, respectively. At the clinoidal level, the mean directions of aneurysms were 76 degrees in six lesions unassociated with branching arteries (13%), 43 degrees in 16 OphA lesions (35%), and -11 degrees in 24 SHA ones (52%). All aneurysms at the infraclinoidal level arose at the origin of the SHAs, with a mean direction of -29 degrees, and most of these were embedded in the carotid cave. CONCLUSIONS: Aneurysms arising from the SHA can be distinguished from those not located at an arterial division by cerebral angiography, because SHA lesions are usually located at the medial or inferomedial wall of the internal carotid artery at the clinoidal or infraclinoidal level. Their distribution correlates well with the reported distribution of SHA origins. The carotid cave aneurysm is a kind of SHA lesion that originates at the most proximal intradural CA.

Adult↗
PubMed2002

Compartments in arteriovenous malformation nidi demonstrated with rotational three-dimensional digital subtraction angiography by using selective microcatheterization. Report of three cases.

Although in several histological studies of arteriovenous malformation (AVM) nidi the presence of compartments has been documented, no clinical study has been published. The present study was conducted to determine the presence of nidus compartments in clinical cases by using a new radiographic method. Two patients with unruptured and one with a ruptured AVM (all Spetzler-Martin Grade III) were studied. A microcatheter was superselectively introduced into each of two or three feeding arteries of the AVMs under three-dimensional (3D) angiographic guidance to obtain 3D images of the nidus by using rotational digital subtraction angiography. On 3D images the different feeding arteries were found to be independent from one another, which allowed the authors to confirm the presence of compartments. On the other hand, separate feeding arteries often had a common draining vessel. Compartments in AVM nidi were demonstrated by a novel rotational 3D angiographic procedure by using superselective microcatheterization, which should be useful for designing treatment strategies for large and complex AVMs.

Angiography, Digital Subtraction↗
PubMed2002

[Analysis with magnetic resonance imaging of lesions in cerebral achromatopsia].

PURPOSE: To localize the lesions associated with cerebral achromatopsia. METHODS: We examined 20 patients with homonymous hemianopsia caused by cerebral infarction(17 men and 3 women aged 49 to 81 years; mean age, 65.1 years). Ishihara plates, standard pseudoisochromatic plates(part 2) and the panel D-15 test were used to examine color perception. Color matching tasks and color naming tasks were used to test color recognition. We tried to apply functional magnetic resonance imaging(fMRI) to lesion analysis in the brain. RESULTS: Cerebral achromatopsia was diagnosed in four patients. The analysis showed that lesions in the infracalcarine area(Brodmann's area 18 and 19) were associated with cerebral achromatopsia. Additionally, the lesions associated with failure of the panel D-15(PD-15) test were located more anterior than the lesions associated with failure of Ishihara plates. CONCLUSION: We show evidence that lesions in the anterio-ventral temporo-occipital area are associated with cerebral achromatopsia. This result is in accord with past observations(autopsy, fMRI and positron emission tomography).

Aged↗