Biomedical subjects

T Shuin

Publications and source records attributed to T Shuin.

At least 73 records · Page 4Linked to original sources

PubMed1998

Overexpression of c-Met/hepatocyte growth factor receptors in human prostatic adenocarcinoma.

Hepatocyte growth factor (HGF) and c-met proto-oncogene product (c-Met) have varied biological functions in different tissues and have been implicated in mitogenic, motogenic and morphogenic responses in both organ regeneration and carcinogenesis. Some studies have suggested that the overexpression of c-Met and epidermal growth factor receptor (EGFR) are associated with growth advantage, while transforming growth factor-beta receptor II (TGF beta R II) is associated with growth disadvantage of human prostatic adenocarcinoma. However, it is unclear if the expression of c-Met correlates with the expression of EGFR and TGF beta R II, and with the proliferative status of human prostatic adenocarcinoma. Using immunohistochemical staining with anti-c-Met (C-12), anti-EGFR (NCL-EGFR) and anti-TGF beta R II (L-21) antibodies, we determined the frequency of expression of c-MET, EGFR, and TGF beta R II respectively in a series of 134 radical prostatectomy specimens. We evaluated the relationship between the expression of these receptors and clinicopathological characteristics. Overall, c-Met immunostaining was detected in 54 of 134 (40.3%) cases, EGFR in 45 (33.6%) and TGF beta R II in 64 (48.4%). The overexpression of c-Met was significantly more common in poorly differentiated (P < 0.0001) and in the diffusely infiltrated specimens (P < 0.0005). In contrast, TGF beta R II was significantly overexpressed in the well differentiated specimens (P < 0.0001) and associated negatively with c-Met (P < 0.0001). Overall, these data suggest that c-Met/HGF receptor and TGF beta R II overexpression may be involved in the differentiation of human prostatic adenocarcinoma, c-Met with de-differentiation and TGF beta R II with differentiation.

Adenocarcinoma↗

PubMed1998

[A case of congenital mesoblastic nephroma in adulthood].

A 20-year-old man was referred to our hospital with a complaint of asymptomatic macrohematuria. A diagnosis of a right renal tumor was made after several radiographic examinations and right radical nephrectomy was performed. Histopathologically the tumor was a congenital mesoblastic nephroma. Congenital mesoblastic nephroma is a relatively rare renal tumor predominantly of childhood. Occurrence in adults is exceedingly rare and 18 cases have been reported to date.

Adult↗

PubMed1997

Simultaneous determination of creatinine, creatine, and guanidinoacetic acid in human serum and urine using liquid chromatography-atmospheric pressure chemical ionization mass spectrometry.

A rapid and direct method for simultaneous determination of creatinine, creatine, and guanidinoacetic acid in biological samples has been developed by using column liquid chromatography-mass spectrometry (LC/APCI-MS). The determinations of creatinine, creatine, and guanidinoacetic acid in the samples of human urine and serum were carried out by scanning the [M + H]+ ions of each compound. The recoveries of authentic compounds were 93.87 +/- 6.00% (n = 5) for creatinine, 94.80 +/- 8.93% (n = 5) for creatine, and 90. 92 +/- 7.96% (n = 5) for guanidinoacetic acid after ion-exchange resin treatment. The content of creatinine in human urine and serum was also measured by the Jaffé method, a common method of determination of creatinine currently used in hospitals. The contents of creatinine, creatine, and guanidinoacetic acid obtained using LC/APCI-MS coincided well with those reported in previous papers.

Atmospheric Pressure↗

PubMed1997

Somatic mutations of the von Hippel-Lindau tumor suppressor gene and loss of heterozygosity on chromosome 3p in human glial tumors.

Molecular genetic analysis of von Hippel-Lindau tumor suppressor gene (VHL gene) was performed on 38 tissues of human glial tumors (ependymoma, 1; astrocytoma, 6; oligodendroglioma, 1; oligoastrocytoma, 2; anaplastic oligoastrocytoma, 3; anaplastic astrocytoma, 14; glioblastoma multiforme, 11). Somatic DNAs extracted from frozen tumor specimens were examined by single-strand conformational polymorphism analysis and direct sequencing. In addition, loss of heterozygosity (LOH) on chromosome 3p in 15 glial tumor cases, lymphocyte DNAs of which were available, was examined by use of 10 microsatellite probes and two polymorphism markers for the VHL gene. Two cases of low-grade gliomas showed somatic sense mutations in exon 3 of the VHL gene, and 6 of 15 cases (40.0%) showed LOH of chromosome 3p. The VHL gene-mutated cases also showed LOH. The retention of heterozygosity and high pathological grade of glial tumors were correlated significantly. In addition, Kaplan-Meier survival analysis for patients with glial tumors showed that patients with LOH had a significantly longer survival time than those without LOH. These results suggest that somatic mutations on 3p, including the VHL gene, may be involved in tumorigenesis of some low-grade glial tumors.

Adult↗

PubMed1997

[A case of Cushing's syndrome due to bilateral multiple adrenal adenomas].

We report a case of Cushing's syndrome due to bilateral adrenal adenomas. A 45-year-old woman was found to have Cushing's syndrome during the course of treatment for diabetes mellitus. The diagnosis of Cushing's syndrome was based on the absence of a diurnal rhythm in plasma cortisol and failure to suppress plasma cortisol by 1 or 4 mg of dexamethasone. The plasma level of adrenocorticotropic hormone (ACTH) was below the normal range, and plasma cortisol responded normally to rapid ACTH injection. Abdominal computed tomography revealed bilateral adrenal tumors. Bilateral uptake of radiocholesterol by the adrenal cortex was observed in adrenal scintigraphy. Bilateral adrenalectomy was performed. Microscopic examination and analysis of steroid contents by high performance liquid chromatography showed that the tumor was cortisol-producting adenoma.

Adenoma↗

PubMed1997

[Microscopic foci of urachal carcinoma in an incidentally detected urachal cyst: a case report].

A 33-year-old man who had been treated for chronic prostatitis was diagnosed to have urachal cysts by transabdominal ultrasonography. Cystoscopy revealed protuberance at the dome of the bladder. Computerized tomography scan and magnetic resonance imaging showed the mass to be mostly cystic but partly solid. Resection of the urachal cysts and partial cystectomy were performed. Histopathologically, most cysts had a normal cylindrical epithelium with retention of mucinous substance. However, several small cysts contained epithelial cells resembling tubulo-villous adenoma and showing mitotic figures. This case was concluded as urachal carcinoma detected in its very early stage.

Adenocarcinoma↗

PubMed1997

[Localized polyarteritis nodosa presenting as epididymal mass: a case report].

A 31-year-old man was admitted with a mass in the left scrotum. On palpation, the mass was elastic hard and hen's egg-sized. It was impossible to discriminate between testis and epididymis. Left high orchiectomy was performed under the diagnosis of left testicular tumor. Histopathologically, distinct arteritis was demonstrated in the epididymis. Since the patient showed no evidence of systemic disease or serological abnormalities, he was diagnosed to have localized polyarteritis nodosa.

Adult↗

PubMed1997

Cyclin A overexpression in carcinoma of the renal pelvis and ureter including dysplasia: immunohistochemical findings in relation to prognosis.

Several in vitro studies have shown that cyclin A gene alteration in the cell cycle plays an important role in carcinogenesis. We immunohistochemically examined the expression of cyclin A protein in 120 patients with transitional cell carcinoma (TCC) of the renal pelvis and ureter, including adjacent dysplastic lesions to determine their significance for the tumor behavior and patient prognosis. Cyclin A immunostaining of the nucleus was observed in 29 tumors (24.2%). Furthermore, 17 cyclin A-positive tumors (58.6%) had dysplastic lesions positive for cyclin A antibody. The prevalence of cases exhibiting cyclin A staining was higher in the high grade (P < 0.01) and invasive tumors (P < 0.05) than in the other types of tumors. In the selected 117 cases, patients whose TCCs expressed a high level of cyclin A protein had a significantly poorer prognosis than those without cyclin A expression (P < 0.01). These in vivo findings provide the first evidence for frequent and redundant cyclin A protein overexpression in TCC and suggest that cyclin A overexpression is related to the tumor behavior and patient prognosis. In addition, our observations indicate that overexpression of cyclin A may be one of the early events, at least in some cases, in the carcinogenesis of TCC.

Aged↗

PubMed1996

Differential effects of overexpression of PKC alpha and PKC delta/epsilon on cellular E2F activity in late G1 phase.

Introduction of a reporter gene containing E2F binding sites linked to the luciferase gene permitted us to detect transient cellular E2F activity in late G1 phase rat 3Y1 fibroblasts. Overexpression of three major protein kinase C (PKC) isozymes expressed in 3Y1 cells caused differing effects on E2F activity depending on the isozymes overexpressed. Overexpression of PKC alpha inhibited E2F activity while the overexpression of PKC delta or PKC epsilon enhanced it, suggesting that these PKC isozymes play different roles in the regulation of E2F activity. Consistent with previous findings that the activation of PKC by TPA in late G1 phase results in the inhibition of DNA synthesis (Huang, C., and Ives, H.E., 1987, Nature 329, 849-850), the addition of TPA in late G1 phase specifically inhibited E2F activity. Overexpression of PKC isozymes resulted in an enhancement of the TPA-induced inhibition of E2F in late G1 phase. This enhancement was observed for all three PKC isozymes examined, suggesting that these PKC isozymes all are potent mediators of the TPA-induced inhibition of E2F activity in late G1 phase.

Animals↗

PubMed1996

Von Hippel-Lindau tumour suppressor gene. Localization of expression by in situ hybridization.

Inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene is responsible not only for VHL disease, but also for sporadic renal cell carcinoma and cerebellar haemangioblastoma. The distribution of VHL gene expression in the mouse embryo was recently studied by in situ hybridization, along with human VHL in 14-week-old fetal kidney: there was widely distributed expression in the former and expression in the tubules and blastema in the latter. Adult human tissue and other fetal organs were not examined. The present paper describes an in situ hybridization study to assess the function of the VHL gene in adult human tissues and in tissues of human fetus at 28 weeks of gestation. The expression of the VHL gene was limited to the adult and fetal brain and kidney, and the adult prostate. Nerve cells in adult and fetal brain were positive, including the cerebellar Purkinje cells. In adult and fetal kidney, the proximal tubular epithelium, the putative origin of the common type of renal cell carcinoma, showed intense signal, whereas the distal nephron, glomeruli, and nephrogenic blastema showed no significant signal. The prostate showed significant signal in the basal epithelium. The adrenal, pancreas, and epidydimis showed no significant signal, in spite of the frequent occurrence at these sites of neoplastic or hamartomatous lesions in VHL disease.

Animals↗

PubMed1996

Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan.

Germline mutation analysis was performed in 469 VHL families from North America, Europe, and Japan. Germline mutations were identified in 300/469 (63%) of the families tested; 137 distinct intragenic germline mutations were detected. Most of the germline VHL mutations (124/137) occurred in 1-2 families; a few occured in four or more families. The common germline VHL mutations were: delPhe76, Asn78Ser, Arg161Stop, Arg167Gln, Arg167Trp, and Leu178Pro. In this large series, it was possible to compare the effects of identical germline mutations in different populations. Germline VHL mutations produced similar cancer phenotypes in Caucasian and Japanese VHL families. Germline VHL mutations were identified that produced three distinct cancer phenotypes: (1) renal carcinoma without pheochromocytoma, (2) renal carcinoma with pheochromocytoma, and (3) pheochromocytoma alone. The catalog of VHL germline mutations with phenotype information should be useful for diagnostic and prognostic studies of VHL and for studies of genotype-phenotype correlations in VHL.

Adrenal Gland Neoplasms↗

PubMed1996

DNA polymerase beta gene mutations in human bladder cancer.

We examined 24 human bladder cancer tissues for possible mutations in the entire coding region of the human DNA polymerase beta gene using polymerase chain reaction analysis, single-strand conformational polymorphism analysis of RNA, and sequence analysis. DNA polymerase beta gene mutations were observed in four of the 24 cases (16.7%) and included three missense point mutations and a single base insertion. The single base insertion was also observed in our previous study of human prostate cancer, suggesting that this region may be a hot spot for mutation of the DNA polymerase beta gene. No clinical or pathological association was found among the four cases that contained the mutation. Three of the four cases with DNA polymerase beta gene mutation had mutations of the p16 or RB genes or loss of heterozygosity of the p53 and APC gene loci. The results of the study presented here suggest that DNA polymerase beta gene mutations, in combination with mutations of tumor suppressor genes, may be involved in certain cases of human bladder cancer.

Base Sequence↗

PubMed1996

Slow induction of gelatinase B mRNA by acidic culture conditions in mouse metastatic melanoma cells.

Gelatinase B has been thought to be a key enzyme for degradation of extracellular matrix in tumour invasion and metastasis. In this study, we examined the effect of acidic culture medium (pH 5.9) on the expression of gelatinase B mRNA in mouse metastatic melanoma cell line (B16-F10). Using reverse transcription-polymerase chain reaction (RT-PCR) analysis, we found that gelatinase B was induced by the acidic culture medium at 24 h, and then gradually diminished to 72 h. By gelatin zymographic analysis, gelatinase B was first detected at 24 h, continued to increase and then reached a plateau at around 48 h. These results suggest that the induction of gelatinase B secretion by acidic culture medium occurs as a result of the gene expression.

Animals↗

PubMed1996

A case of chromophobe renal cell carcinoma associated with low chromosome number and microsatellite instability.

Cytogenetic study in a case of a human chromophobe renal cell carcinoma revealed a hypodiploid chromosome number of 36 with loss of chromosomes 1, 2, 5, 6, 10, 13, 15, 17, 21, and X. The tumor DNA showed microsatellite instability in dinucleotide repeat microsatellite markers. This is the fourth case that has been fully karyotyped and showed a low chromosome number in a chromophobe renal cell carcinoma. Our data in the present study are consistent with those in the literature. It is suggested that human chromophobe renal cell carcinoma may possibly be characterized by tumor cells with low chromosome number or microsatellite instability.

Adult↗

PubMed1996

Bilateral adrenocortical carcinoma showing loss of heterozygosity at the p53 and RB gene loci.

Presented is a rare case of nonfamilial, hormonally nonfunctional adrenocortical carcinoma with synchronous bilateral adrenal involvement. We investigated adrenal and metastatic tumors for loss of heterozygosity affecting four genetic loci containing the tumor suppressor genes p53, RB, DCC, and APC, using polymerase chain reaction and restriction fragment length polymorphism assay. Allelic losses at the p53 and RB loci were detected in all tumor samples, suggesting that the p53 and RB genes are involved in the tumorigenesis of adrenocortical carcinoma.

Adrenal Cortex Neoplasms↗

PubMed1996

Molecular genetic diagnosis of von Hippel-Lindau disease: analysis of five Japanese families.

We analyzed deoxyribonucleic acids from blood samples of five Japanese von Hippel-Lindau (VHL) disease families (three familial cases, two new mutations) for the presence of VHL gene mutations by single-strand conformational polymorphism analysis and direct sequencing. Four of the five families showed germ line mutations in VHL gene, comprising 2 missense mutations, 1 deletion, and 1 splice-site mutation. Two families had VHL gene mutations at exon 1; 1 family at exon 3; and 1 family at the splice-site adjacent to exon 3. Presymptomatic patients were accurately diagnosed by these methods. However, one family did not show a VHL gene mutation in the germ line but showed a somatic mutation at exon 2 in the hemangioblastoma tissue. The consequence of the somatic mutation was a microdeletion leading to a frameshift mutation. Our study is the first report of VHL gene analyses of Japanese VHL disease families, and suggests that not only germ line mutation, but also somatic mutation can lead to development of a tumor associated with the VHL disease.

Base Sequence↗

PubMed1996

[The efficacy of ATP sensitivity assay on intravesical prophylactic instillation for superficial bladder cancer].

BACKGROUND: The object of this study is to evaluate the usefulness of the ATP sensitivity assay for appropriate selection of anticancer drugs for prophylactic bladder instillation therapy in patients with superficial bladder cancer. METHODS: The ATP assay was performed using the method reported previously. The anticancer drugs examined were ADM, MMC, THP-ADM and EPI. The 5-year rate of non-recurrence in group A (32 cases) which had been treated using the results of ATP assay, was compared with that of group B (37 cases), for which the ATP assay was not performed. RESULTS: The most sensitive anticancer drug was THP-ADM. The 5-year rate of non-recurrence in group A (80.9%) was significantly higher than that in group B (39.4%) (p < 0.001). Tumor recurrences in group A was observed within 2 years post-operatively in all cases. When the ATP assay was re-performed in 3 cases with recurrent disease, altered antitumor sensitivity was observed. CONCLUSION: These findings suggested that ATP assay was useful for choosing effective anti-cancer drugs for prophylactic instillation, especially for patients with primary or solitary tumor, grade 2 disease or tumor of a certain size (> or = 1 cm). It also appeared that the ATP assay should be performed for patients with primary superficial bladder cancer as a screening test for the selection of drugs for prophylactic instillation therapy.

Administration, Intravesical↗

PubMed1996

Loss of heterozygosity at the p53, RB, DCC and APC tumor suppressor gene loci in human bladder cancer.

PURPOSE: Allelic losses within several tumor suppressor genes have been detected frequently in various types of human cancer. We investigated the roles and possible interactions of the tumor suppressor genes p53, Rb, DCC and APC in bladder cancer. MATERIALS AND METHODS: Loss of heterozygosity (LOH) of these 4 genes was examined in 45 human bladder cancers by polymerase chain reaction and restriction fragment length polymorphism assay. RESULTS: Of the evaluated cases, LOH was seen at P53 in 38%, at Rb in 22%, at DCC in 36% and at APC in 6% of tumors. Loss of heterozygosity at p53 and Rb was predominantly observed in high grade (grade 3) and/or invasive (T2 or greater) tumors, whereas LOH at DCC was present irrespective of tumor grade and stage. Allelic losses at either p53, Rb, DCC or APC were seen in 82% of high grade tumors, but in only 21% of low grade (grade 1 and 2) tumors (p<0.005). Similarly, 71% of invasive tumors had LOH at one or more loci compared with 20% of superficial (Ta and T1) tumors (p<0.005). Interestingly, p53-LOH and Rb-LOH were often observed simultaneously in the same tumor. CONCLUSIONS: These results suggest that loss of the p53, Rb and/or DCC genes is involved in most of the late and some of the early steps of bladder carcinogenesis.

Base Sequence↗