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Y Miyoshi

Publications and source records attributed to Y Miyoshi.

At least 55 records · Page 3Linked to original sources
PubMed2001

[Diagnosis of prostate capsular invasion by pelvic magnetic resonance imaging and serum level of prostate specific antigen].

Transrectal ultrasonography (TRUS), computed tomography (CT), and magnetic resonance imaging (MRI) are employed to diagnose the clinical stage of prostate cancer. However, several cases are diagnosed as pathological stage pT3 after total prostatectomy. We investigated the accuracy of the evaluation of pathologic capsular penetration by preoperative pelvic MRI and preoperative serum PSA level and capsular penetration. The diagnostic accuracy of capsular penetration by MRI was 63.3%. On the other hand, the diagnostic accuracy of capsular penetration by preoperative PSA was 89.7% when its cut off value was 17 ng/ml. We conclude that preoperative serum PSA level could be more useful to diagnose accurately stage of prostate cancer than pelvic MRI.

Aged↗
PubMed2000

Detection of chromosomal aneusomy by fluorescence in situ hybridization in fine-needle aspirates from breast tumors: application to the preoperative diagnosis of breast carcinoma.

BACKGROUND: The authors studied the clinical usefulness of fluorescence in situ hybridization (FISH) analysis of a numerical aberration of chromosomes (aneusomy) using fine-needle aspiration (FNA) samples from patients with breast tumors in the preoperative diagnosis of breast carcinoma. METHODS: FNA samples were obtained from 176 breast tumors and were subjected to conventional cytology and FISH analysis using the centromere probes for chromosomes 1, 11, and 17. Patients with FNA samples that showed aneusomy in at least one of the three chromosomes were diagnosed as positive. RESULTS: Histologic examination revealed 157 malignancies and 19 benign results (10 fibroadenomas, 6 intraductal papillomas, 1 intracystic papilloma, and 2 ADH). The sensitivity, specificity, and diagnostic accuracy were 85.4%, 94.7%, and 86.4%, respectively, for cytology and 90.4%, 100%, and 91.5%, respectively, for FISH. Of 15 breast malignancies that were diagnosed with indeterminate cytology, 13 were diagnosed as positive with FISH analysis (sensitivity, 86.7%). CONCLUSIONS: The results demonstrate that the use of FISH in the diagnosis of FNA samples has a diagnostic accuracy comparable to conventional cytology and is useful in making a definitive diagnosis of malignancy (100% specificity) in patients with indeterminate cytologic results, suggesting that FISH diagnosis can be a good adjunct to conventional cytology.

Adult↗
PubMed2000

Quantitative analysis of estrogen receptor-beta mRNA and its variants in human breast cancers.

We have carried out a quantitative analysis of ER-alpha and ER-beta mRNA expression in normal (n = 11) and breast cancer (n = 112) tissues using a real-time (Taq-Man) PCR assay. Expression of ER-beta mRNA variants has also been studied by triple-primer PCR assay. ER-alpha mRNA levels in normal breast tissues were significantly (p < 0.01) lower than those in ER-positive breast cancers but not significantly different from those in ER-negative breast cancers. However, ER-beta mRNA levels in normal breast tissues were significantly (p < 0.01) higher than those in ER-positive and ER-negative breast cancers. Proportions of ER-beta1 and ER-beta2 mRNA expression among total ER-beta mRNA expression were significantly higher and those of ER-beta5 and ER-beta5; mRNA were significantly lower in normal breast tissues than in ER-positive and ER-negative breast cancers. ER-beta mRNA levels and proportions of ER-beta mRNA variants did not show any significant correlation with age, tumor size, lymph node status and histological grade. Our results demonstrate that ER-alpha mRNA is up-regulated and ER-beta mRNA is down-regulated during carcinogenesis of breast cancers. Changes in proportions of ER-beta mRNA variants are also implicated in this process.

Adult↗
PubMed2000

Acceleration of chromosomal instability by loss of BRCA1 expression and p53 abnormality in sporadic breast cancers.

Correlation of chromosomal instability (CIN) with BRCA1 expression and p53 abnormality was studied in sporadic breast cancers since these genes are implicated in the double strand DNA repair and mitotic checkpoint, and loss of their function is speculated to result in the accumulation of CIN. CIN values (percentage of cells with non-modal chromosomes) were determined by fluorescence in situ hybridization of chromosomes 1, 11, and 17. BRCA1 expression was studied by immunostaining, and p53 abnormality was studied by immunostaining and polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP). CIN values of BRCA1 negative/p53 normal tumors (28.9+/-13.8, n=23) and those of BRCA1 positive/p53 abnormal tumors (27.0+/-2.3, n=3) were not significantly different from those of BRCA1 positive/p53 normal tumors (23.8+/-11.5, n=10). On the other hand, BRCA1 negative/p53 abnormal tumors (41.2+/-12.7, n=23) showed a significant (P<0.01) increase in CIN values than BRCA1 positive/p53 normal tumors. There was no significant association between CIN values and menopausal status, tumor size, histological grade, lymph node status, or estrogen receptor status. These results suggest that BRCA1 down-regulation and p53 abnormality work synergistically to induce CIN in breast cancers, and that clinico-pathological characteristics of breast cancers with high CIN still remain to be established.

Adult↗
PubMed2000

Activation of the beta-catenin gene by interstitial deletions involving exon 3 as an early event in colorectal tumorigenesis.

beta-Catenin has been identified as an oncogene in several tumors including colorectal cancers. beta-Catenin gene is activated by interstitial deletions involving exon 3 in colorectal carcinomas of Japanese population, in contrast to amino acid substitutions detected among Caucasian population. The aim of this study was to examine the type and frequency of beta-catenin gene mutation during early stages of colorectal tumorigenesis. We screened 100 colorectal adenomas for somatic mutations in the beta-catenin gene by single-strand conformation polymorphism method, as well as polymerase chain reaction amplification. In cases with mutations, sequencing analyses and immunohistochemical staining were also performed. Somatic interstitial deletions of 272-413 bp, each of which included all parts of exon 3, were detected in three tumors. However, no adenoma carried missense mutations. We confirmed accumulation of aberrant beta-catenin protein in cytoplasm and nuclei of adenoma cells by immunohistochemical analysis. Our results suggested that activation of the beta-catenin gene by interstitial deletions involving exon 3 might be less frequent compared with frequent alterations of adenomatous polyposis coli (APC) gene, but could be an early event in colorectal tumorigenesis equivalent to APC gene alterations in the Japanese population.

Adenoma↗
PubMed2000

Quantitative analysis of estrogen receptor-alpha and -beta messenger RNA expression in breast carcinoma by real-time polymerase chain reaction.

BACKGROUND: Estrogen action is mediated not only through a classic estrogen receptor (ER) (ER-alpha) but also through a second ER (ER-beta) that has a structure and function similar to ER-alpha. A correlation between ER-beta mRNA expression with ER and progesterone receptor (PR) protein levels as well as prognostic factors remains to be established in breast carcinoma. METHODS: The authors conducted a quantitative analysis of ER-alpha and ER-beta mRNA expression in 116 breast tumors using real-time polymerase chain reaction (PCR), and investigated a possible correlation between ER-alpha and ER-beta mRNA expression and ER and PR status as determined by enzyme immunoassay as well as with various prognostic factors. RESULTS: ER-alpha mRNA levels were significantly (P < 0.01) higher in ER positive compared with ER negative tumors. Conversely, ER-beta mRNA levels were significantly (P < 0.01) lower in ER positive compared with ER negative tumors. Accordingly, the ratio of ER-beta to ER-alpha was significantly (P < 0.01) higher in ER negative compared with ER positive tumors. A subset analysis based on ER and PR status showed that ER-beta mRNA levels as well as the ratios of ER-beta to ER-alpha mRNA level were highest in ER negative and PR negative tumors (P < 0.05). ER-alpha mRNA levels were significantly (P < 0.05) higher in postmenopausal compared with premenopausal tumors. Histologic Grade 3 tumors showed a significant decrease in ER-alpha mRNA levels compared with Grade 1 and 2 tumors (P < 0.01 and P < 0.05, respectively). No significant correlation between ER-alpha and ER-beta mRNA levels and histologic type, tumor size, or lymph node status was observed. CONCLUSIONS: An absolute and relative increase in ER-beta mRNA levels in ER negative and PR negative breast tumors, which rarely respond to endocrine therapy, suggests the possible involvement of up-regulation of ER-beta mRNA in the development of estrogen-independent tumors.

Adult↗
PubMed2000

Breast cancer risk associated with polymorphism in CYP19 in Japanese women.

Screening of the entire coding and major promoter regions of the CYP19 gene identified two novel polymorphisms at codon 39 (Trp to Arg) and codon 408 (silent) in addition to those reported previously at codon 264 (Arg to Cys) and intron 4 [tetranucleotide (TTTA) simple tandem repeat]. A case-control study was conducted in order to see whether or not these polymorphisms were associated with breast cancer risk in Japanese women. Homozygous and heterozygous carriers of the variant allele Arg at codon 39 showed a significantly decreased risk of breast cancer (OR=0.39, 95%C.I.=0. 17-0.89). On the other hand, homozygous carriers of the allele with 10 or more TTTA repeats at intron 4 showed a trend toward an increase (OR=1.80, 95%C.I.=0.97-3.36) in breast cancer risk. Other polymorphisms were found not to be associated with breast cancer risk. These results suggest that the CYP19 polymorphisms at exon 39 and intron 4 would be useful for selecting Japanese women at a high risk of breast cancer.

Adult↗
PubMed2000

Isolation and characterization of a novel human gene, DRCTNNB1A, the expression of which is down-regulated by beta-catenin.

Beta-catenin plays significant roles in cell-to-cell adhesion and the Wnt/Wg signal transduction pathway. Accumulation of this protein in the cytoplasm and nucleus as a result of mutations of the adenomatous polyposis coli tumor suppressor gene or of the beta-catenin gene itself is often seen in a wide variety of tumors including carcinomas of the colon, liver, uterus, and brain. Interaction of accumulated beta-catenin with Tcf/Lef transcription factors is known to deregulate expression of some downstream genes, but the precise mechanisms whereby beta-catenin contributes to carcinogenesis remain to be disclosed. Here we report isolation of a novel murine gene, Drctnnb1a (down-regulated by Ctnnb1, a), the expression of which was experimentally down-regulated in response to the activated form of beta-catenin. To investigate a possible role of DRCTNNB1A in cancers, we also isolated the human homologue, DRCTNNB1A, the deduced product of which was 91% identical to the murine protein. The transcript was expressed in all human tissues examined, and we assigned the genomic location of DRCTNNB1A to chromosomal band 7p15.3 by in situ hybridization. Expression of DRCTNNB1A in SW480 colon cancer cells was significantly increased in response to reduction of intracellular beta-catenin by adenovirus-mediated transfer of the beta-catenin-binding domain of the adenomatous polyposis coli gene into the cells. Furthermore, we documented reduced expression of DRCTNNB1A in 12 of 15 primary colorectal cancers examined, compared with corresponding adjacent noncancerous mucosae. Our results implied that DRCTNNB1A is one of the genes involved in the beta-catenin-Tcf/Lef signaling pathway, and that reduced expression of DRCTNNB1A may have some role in colorectal carcinogenesis.

Animals↗
PubMed2000

Fluorescence in situ hybridization evaluation of c-myc and androgen receptor gene amplification and chromosomal anomalies in prostate cancer in Japanese patients.

BACKGROUND: Oncogene amplification and chromosomal anomalies are found in many solid tumors and are often associated with aggressiveness of cancer. We evaluated the frequency and the association of c-myc and androgen receptor (AR) gene amplification and gain of chromosome 8 or X in prostate cancer in Japanese patients. METHODS: We examined a total of 42 prostate cancer specimens, using fluorescence in situ hybridization (FISH). Dual-labeling hybridization with a directly labeled centromere probe for chromosome 8 or X together with a probe for the c-myc or AR locus was performed. RESULTS: Gain of chromosome 8 was identified in 54.8% of specimens and was associated with Gleason sum and nuclear anaplasia in untreated prostate cancers. c-myc gene amplification was found in 14.3% of specimens. Gain of chromosome X was identified in 42.9% of specimens. AR gene amplification was detected in 0 of 37 untreated prostate cancers, but in 1 of 5 hormone-refractory prostate cancers. CONCLUSIONS: Our results suggest that c-myc and AR gene amplification and gain of chromosome 8 or X may be associated with the development and progression of prostate cancers. These results obtained in Japanese cases are consistent with the results observed in prostate cancer in Western countries.

Chromosome Aberrations↗
PubMed2000

K-ras point mutation in the nerve plexuses around the superior mesenteric artery in resectable adenocarcinoma of the pancreatic head: distribution pattern and related factors.

BACKGROUND: Adenocarcinoma of the pancreas is likely to spread into the nerve plexuses around the superior mesenteric artery (SMA) at a microscopic level. Since there has been no detailed report on how minute cancer invasion is distributed among the peri-SMA plexuses or which cases are more vulnerable to such an event, it has long been controversial how to treat this area when resecting the pancreatic head cancer. HYPOTHESIS: The K-ras mutation assay is more sensitive than the conventional histologic diagnosis in detecting minute cancer invasion around the SMA. DESIGN: Prospective consecutive series. SETTING: Cancer center hospital. PATIENTS AND METHODS: The entire circle of the peri-SMA tissues was obtained from 24 patients who had received an extended pancreatectomy for adenocarcinoma of the pancreatic head. They were divided into right and left hemicircular samples (48 samples), and each sample was used for both histologic and genetic diagnoses. Since all patients' primary tumors were positive for point mutation at codon 12 of the K-ras gene, the presence or absence of the mutation was determined for the peri-SMA plexuses using the mutant allele specific amplification method. RESULTS: Compared with results of the histologic examination, the K-ras mutation assay was more sensitive in detecting positive findings in the peri-SMA plexuses (12 samples from 9 patients). According to the distribution of the K-ras mutation into the right- and left-half samples, 24 patients were classified into the following 4 patterns (right/left): negative/negative in 15 patients; positive/negative in 6 patients; positive/positive in 3 patients; and negative/positive in 0 patients. In 3 patients who showed a positive/positive pattern in the genetic diagnosis, their right-half samples included more cancer cells that were detectable by routine microscopy. There was no relation between K-ras mutation and lymphatic invasion, while K-ras mutation was particularly related with the invasion of portal vein (P =.04) and posterior peripancreatic tissues (P =.002). All 3 patients with K-ras mutation in bilateral plexuses were classified by the TNM staging system as T4 using Union Internationale Contre le Cancer classification. CONCLUSIONS: The K-ras mutation (at codon 12) assay indicated a simple and regular pattern of cancer extension into the nerve plexuses around the SMA from adenocarcinoma of the pancreatic head: (1) The left half of the plexus was unlikely to be involved by cancer in cases in which the right half was intact. (2) Cancer extension into the peri-SMA plexuses occurred after the posterior confine of the pancreas had been involved by direct invasion from the primary pancreatic tumor. (3) The left half was not involved in cancerous tumors classified as T1 to T3 but was occasionally involved in those classified as T4 tumors. These data seem to provide a useful indicator of some additional treatments (resection, irradiation, etc) for the peri-SMA region when a locally advanced pancreatic head cancer is treated with a curative intent.

Adenocarcinoma↗
PubMed2000

Isolation and characterization of a novel TP53-inducible gene, TP53TG5, which suppresses growth and shows cell cycle-dependent transition of expression.

Through a strategy of direct cloning of TP53-binding DNA sequences from human genome DNA, we have identified a novel TP53-target gene, termed TP53TG5 (TP53-target gene 5). This gene, localized to chromosome band 20q13.1 by fluorescence in situ hybridization, encodes a 290-amino-acid peptide with no significant homology with any known proteins in the public database. A colony-formation assay using human glioblastoma cell line T98G, which lacks wild-type TP53 and expresses no endogenous TP53TG5, revealed a growth-suppressive effect of the TP53TG5 gene product. Furthermore, immunohistochemical studies, following transfection of T98G with plasmid designed to express green fluorescent protein-fused TP53TG5, revealed cell cycle-dependent intracellular localization of this protein. Our results suggest that functional studies of TP53TG5 may provide new insights into the complex physiological activities of TP53.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Isolation of a novel gene on 8p21.3-22 whose expression is reduced significantly in human colorectal cancers with liver metastasis.

Metastasis, a major factor contributing to poor prognosis of cancer patients, is caused by a complex series of events that involve many genes. To investigate this process, we analyzed by differential display three cell lines that had been established from a murine colon adenocarcinoma (colon 26), NL4, NL17, and NL22, each of which possessed a different potential for metastasis in mice. We report here the identification of a novel gene, ream (reduced expression associated with metastasis), which showed significantly lower expression in NL17 and NL22 with a high potential for metastasis than in NL4 without a metastatic potential. The human counterpart of murine ream expressed two sizes of transcript, 4.4 kb and 1.8 kb, both encoding the same 367-amino acid peptide, which appeared to contain four membrane-spanning regions. The cDNA showed no significant homology to any known genes in the public database. Human REAM was found to lie within an 800-kb segment of 8p21.3-22, where we had previously identified a commonly deleted region in colorectal and hepatocellular carcinomas. Its expression was reduced in more than half of the human colorectal cancers we examined, particularly in advanced stages with liver metastasis. Furthermore, we identified somatic mutations of this gene in a colorectal cancer, a hepatocellular carcinoma, and a nonsmall lung cancer among 111 human tumors of various stages examined.

Adenocarcinoma↗
PubMed2000

Ulnar artery graft for myocardial revascularization.

We present a 60-year-old man who underwent coronary artery bypass grafting using an ulnar artery as one of the grafts intended to release angina pectoris. Previously, his right leg had been amputated following a traffic accident. The blood supply of his left leg was reduced due to atherosclerotic stenotic change (left ankle pressure index 0.6). He had been under treatment for severe diabetes mellitus for 4 years. Coronary angiography revealed severe stenosis in the triple coronary artery system. Immediate myocardial revascularization was considered necessary. We considered that saphenous vein grafts and bilateral internal thoracic artery grafts were unsuitable for this patient. Moreover, Allen's test was positive in the bilateral forearms. Coronary artery bypass surgery consisted of left internal thoracic artery grafting to the left anterior descending artery, right gastroepiploic artery grafting to the right coronary artery, and left ulnar artery grafting to the diagonal branch. No myocardial or hand complications were observed after surgery. Following a review of the Japanese literature, we conclude that our case is the first report of an ulnar artery graft for coronary artery bypass grafting in Japan.

Angina Pectoris↗
PubMed2000

Correlations of elevated levels of hexacosanoate in erythrocyte membranes with risk factors for atherosclerosis.

We analyzed erythrocyte membrane C26:0 from 504 volunteers by high-performance liquid chromatography. The associations between the elevated levels of erythrocyte membrane C26:0 (0.20 or greater than 0.20%) and sex, obesity (body mass index> or =26.4), smoking (> or =20 cigarettes per day), present illnesses and past diseases were examined with the chi(2) test. The correlations among age and the levels of erythrocyte membrane C26:0, plasma total cholesterol, triglycerides, LDL cholesterol and HDL cholesterol were analyzed using Spearman's correlation coefficient. Moreover, the frequencies of high levels of erythrocyte membrane C26:0 were examined in male and female subjects divided into seven age groups. The elevated levels of erythrocyte membrane C26:0 were significantly more frequent in male subjects than in females, and were closely associated with obesity, smoking, and atherosclerosis-related diseases of present illnesses. The levels of erythrocyte membrane C26:0 were highly correlated with age and the levels of plasma total cholesterol, triglycerides and LDL cholesterol, and inversely with those of HDL cholesterol. The frequency of high levels of erythrocyte membrane C26:0 in male subjects was greater than that in female subjects in all of the seven age groups. Elevated levels of erythrocyte membrane C26:0 may be closely related with atherosclerosis.

Adult↗
PubMed2000

beta(2)-glycoprotein I deficiency: prevalence, genetic background and effects on plasma lipoprotein metabolism and hemostasis.

beta(2)-glycoprotein I (beta(2)-GPI=apolipoprotein H) is an important autoantigen in patients with the antiphospholipid syndrome. It also plays a role in lipoprotein metabolism, such as anti-atherogenic property, triglyceride removal, and enhancement of lipoprotein lipase. Serum beta(2)-GPI concentration of 812 apparently healthy Japanese individuals was measured by sandwich EIA. Two families with complete beta(2)-GPI deficiency were identified. In one family, all affected had increased serum LDL-cholesterol levels or smaller particle sizes of LDL, while the other had no apparent abnormality in lipid metabolism. Individuals investigated had no history of thrombosis or overt abnormalities in hemostatic tests. A thymine corresponding to position 379 of the beta(2)-GPI cDNA was deleted in every beta(2)-GPI deficient individual. The incidence of this heterozygous deficiency determined by RFLP was 6. 3% in Japanese and none in Caucasians. Heterozygotes had significantly lower concentrations of serum beta(2)-GPI than did those without the mutation, yet no significantly different lipid profiles, such as total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, apoA-I, apoB and Lp(a), were observed. A low concentration of beta(2)-GPI seemed not to be associated with apparent abnormality in lipoprotein metabolism.

Adult↗
PubMed2000

Genetic polymorphism in CYP17 and breast cancer risk in Japanese women.

A case-control study was conducted to investigate the association of two genetic polymorphisms (1931T/C and 1951G/A) in the promoter region of the CYP17 gene with breast cancer risk in Japanese women. No significant association was observed between CYP17 polymorphism(1951G/A) and breast cancer risk (odds ratio (OR) = 1.71, 95% confidence interval (CI): 0.28-1.84). In contrast, a significant increase in breast cancer risk (OR= 1.82. 95% CI: 1.07-3.12) was observed in CYP17(1931C/C) homozygotes compared with CYP17(1931T/C) heterozygotes and CYP17(1931T/T) homozygotes when women aged > or = 55 years were considered, but such a significant increase was not observed when women aged < or = 54 years were considered (OR = 0.96, 95% CI: 0.56-1.63). These results suggest that CYP17 polymorphism(1931T/C) would be useful in the selection of Japanese women at a high risk for developing breast cancer at the age of > or = 55 years.

Adult↗