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T Shuin

Publications and source records attributed to T Shuin.

At least 55 records · Page 3Linked to original sources
PubMed2000

Missense mutation of the hMSH6 and p53 genes in sporadic urothelial transitional cell carcinoma.

Functional defects in DNA mismatch repair genes have been shown to be associated mainly with hereditary human malignancies. We examined genomic DNA from 88 sporadic transitional cell carcinomas (TCCs) of the urinary tract for mutations in hMSH6 gene by polymerase chain reaction and direct sequencing analysis. Mutational status of p53 gene was also studied as a potential target of genetic instability secondary to hMSH6 dysfunction. A total of 5 cases (5.7%: 5/88) displayed hMSH6 mutations all consisted of transition and located in exon 4, including three cases with missense mutation and two without change of corresponding amino acid. These three tumors with hMSH6 missense mutation had no microsatellite instability with five microsatellite markers tested. p53 gene mutations were detected in 22 cases (25.0%: 22/88). No tumors with p53 mutation had any hMSH6 missense mutations. Compared to the cases without hMSH6 alterations, the three patients with hMSH6 alterations had more frequent additional primary cancer (P<0.05). These findings provide the first in vivo evidence for the type of alterations and frequency of possible involvement of the hMSH6 mutations in sporadic type urothelial TCCs.

Aged↗
PubMed2000

[Von Hippel-Lindau disease].

The von Hippel-Lindau (VHL) disease is a multitumor syndrome characterized by CNS hemangioblastoma, pheochromocytoma and renal cell carcinoma. The VHL disease gene is a putative tumor suppressor gene responsible for VHL disease. VHL disease without pheochromocytoma (pheo) and those with pheo are classified as type 1 or type 2, respectively. Germline missense mutations are clustered in 4 regions in the VHL gene. The VHL protein is now regarded as a one of the key protein for ubiquitination and further degradation of certain transcription factors such as hypoxia inducible factor (HIF). Since almost of germline mutations are detectable, presymptomatic diagnosis of the VHL disease with DNA analyses is important to improve the prognosis of VHL disease.

Follow-Up Studies↗
PubMed2000

Detection of circulating cancer cells with von hippel-lindau gene mutation in peripheral blood of patients with renal cell carcinoma.

Mutations of the von Hippel-Lindau (VHL) tumor suppressor gene have been detected in up to 60% of sporadic clear cell renal carcinomas (RCCs). Even patients with RCCs believed to be curable with radical nephrectomy sometimes develop distant metastasis 5-10 years after surgery, suggesting hematogenous circulation of cancer cells. Useful tumor markers have not yet been established for RCC. To detect patients at high risk of metastasis after surgery, we developed a highly sensitive and specific nested reverse transcription-PCR method using VHL gene mutation to detect circulating cancer cells. We screened 29 sporadic clear cell RCCs from patients for mutations of the VHL gene by direct sequencing. We next examined blood samples from patients with the VHL gene mutation using mutation-specific nested reverse transcription-PCR. Somatic mutations were detected in 20 of 29 (69.0%) sporadic clear cell RCCs. The VHL gene mutations were detected in peripheral and/or renal venous blood from 15 of 20 (75%) patients. The mutations were detected in the peripheral blood in 2 of 17 (11.8%) patients before surgery, 6 of 16 (37.5%) patients within 24 h after surgery, 3 of 16 (18.8%) patients on day 7 after surgery, and 2 of 11 (18.2%) patients on day 30 after surgery. In seven of nine (77.8%) patients, mutations were detected in renal venous blood during surgery. These findings indicate the presence of circulating cancer cells with VHL gene mutation. Although much larger studies are needed to determine the clinical significance, our study shows that this technique is feasible for detecting circulating RCC cells.

Adult↗
PubMed2000

The prognostic value of angiogenesis factor expression for predicting recurrence and metastasis of bladder cancer after neoadjuvant chemotherapy and radical cystectomy.

To determine the prognostic value of angiogenesis factor expression for patients with muscle-invasive transitional cell carcinoma (TCC) of the bladder treated with neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) chemotherapy and radical cystectomy, we evaluated the expression of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and interleukin 8 (IL-8) by in situ hybridization, and we determined microvessel density (MVD) by immunohistochemistry. These factors were evaluated in 55 biopsy specimens prior to therapy and in the cystectomy specimens of 51 patients after completion of therapy. By univariate analysis, VEGF expression and MVD in the biopsy specimens were significant predictors of disease recurrence. By multivariate analysis, only VEGF expression was an independent prognostic factor. Pathological stage, bFGF expression, and MVD in the cystectomy specimens after therapy were all independent prognostic factors for disease recurrence. The results of this exploratory study indicate that the expression levels of VEGF and bFGF as indicated by in situ hybridization and MVD as indicated by immunohistochemistry identify patients with muscle-invasive TCC who are at high risk of developing metastasis after aggressive therapy with systemic M-VAC chemotherapy and radical cystectomy.

Adult↗
PubMed2000

Effect of cisplatin treatment on the urinary excretion of guanidinoacetic acid, creatinine and creatine in patients with urinary tract neoplasm, and on superoxide generation in human neutrophils.

Production of guanidinoacetic acid, a precursor of creatinine is known to be reduced by metabolic disturbance when kidney function is damaged, and thus it may be a sensitive marker of renal damage. Therefore, the urinary levels of guanidinoacetic acid, creatinine and creatine from patients with urinary tract neoplasm who received cisplatin treatment were measured by liquid chromatography-mass spectrometry. Following the administration of cisplatin, the urinary excretion of guanidinoacetic acid decreased significantly, and the low concentration was maintained for at least five days. The concentrations of creatinine and creatine gradually decreased until the third day after cisplatin administration, and slightly increased on the fifth day. As superoxide might be concerned in renal damage by cisplatin, the effect of cisplatin on superoxide generation was also investigated using human neutrophils. Cisplatin significantly enhanced phorbol 12-myristate 13-acetate-induced superoxide generation in a concentration-dependent manner, but had no effect on the superoxide generation induced by N-formyl-methionyl-leucyl-phenylalanine and arachidonic acid. The superoxide generation increased by cisplatin was inhibited by staurosporine, an inhibitor of protein kinase C, but was rather enhanced by genistein, an inhibitor of protein tyrosine kinase.

Adult↗
PubMed1999

Direct interaction of the beta-domain of VHL tumor suppressor protein with the regulatory domain of atypical PKC isotypes.

VHL tumor suppressor protein contains two domains, alpha and beta. The alpha-domain is involved in the formation of a large protein complex suggested to be involved in ubiquitin-mediated protein degradation. However, the role of the beta-domain, which may recognize the target proteins for protein degradation, remains unknown. Here we report that the beta-domain interacts directly with atypical PKC isotypes, PKCzeta and PKClambda. Further, the regulatory domain of aPKC is sufficient for this direct protein-protein interaction. Since aPKC isotypes have been implicated in the regulation of cell growth and apoptosis, these results suggest that aPKC isotypes are potential direct target of the VHL beta-domain.

Amino Acid Sequence↗
PubMed1999

Human mismatch repair gene (hMSH2) product expression in relation to recurrence of transitional cell carcinoma of the urinary bladder.

BACKGROUND: Several convincing studies have shown that the hMSH2 gene plays major roles in mismatch repair by recognizing mismatched bases and preventing mutations during DNA replication. Loss of this function may result in the accumulation of DNA replication errors or even the mutator phenotype (which may be responsible for the multiple mutations required for multistep carcinogenesis), and it has been found to affect the prognosis of patients. Thus, the authors felt that it would be of interest to study the expression patterns of hMSH2 protein in malignant tumors and to assess the correlation of hMSH2 protein to various clinical and pathologic features in these patients. METHODS: The authors examined the expression patterns of hMSH2 protein in 115 patients with transitional cell carcinoma (TCC) of the urinary bladder by immunohistochemical technique using monoclonal antibody to hMSH2 protein. RESULTS: The group in which hMSH2 was preserved (>20% of nuclei were positive for staining by anti-hMSH2 antibody) included 86 of 115 (75%) of the TCCs, whereas the remaining 29 cases (25%) belonged to the group in which hMSH2 was preserved (< or = 20% of tumor nuclei were positive), including 2 negative cases. Univariate analysis indicated that reduced expression of hMSH2 protein was significantly more frequent in high grade tumors than in low grade tumors (P = 0.04). Furthermore, statistical multivariate analysis revealed that hMSH2 reduction was significantly related to the recurrence (P = 0.02). CONCLUSIONS: These results suggest that abnormal expression of hMSH2 protein might be involved in tumorigenic processes and in the progression of some TCCs, and that the loss of hMSH2 protein expression might be a useful predictor of recurrence of TCC.

Aged↗
PubMed1999

Genetic instability did not lead to p53 mutations in an extremely early-onset breast cancer in a cancer-prone family.

BACKGROUND: A positive family history is a major contributor to risk of development of breast cancer. METHODS: Somatic and germ line mutations of p53 and genetic instability were evaluated for an extremely early-onset breast cancer case in a cancer-prone family. RESULTS: The mode of inheritance in this case was clearly autosomal dominant. DNA replication error was recognized by detecting microsatellite allelic alterations. However, mutations of p53 were not found at either somatic or germ-line level. CONCLUSION: These genetic studies suggest that an increased genetic instability did not lead to p53 gene mutations in this breast cancer patient.

Adult↗
PubMed1999

[Molecular genetic mechanism of hereditary human kidney cancer development].

Here we reviewed the molecular genetic mechanism in the development of 4 types of human hereditary kidney cancers. These include von Hippel-Lindau (VHL) disease, hereditary papillary renal carcinoma, familial renal cancers with translocation of chromosome 3, and Tuberous sclerosis. Loss of function of the VHL disease gene is responsible for the von Hippel-Lindau disease and major portion of sporadic clear cell renal carcinoma. Activated c-Met oncogene is responsible for the development in some cases of hereditary papillary renal cell carcinomas and sporadic papillary renal carcinomas. There are several cases of familial renal carcinoma in that translocations of chromosome 3 p are demonstrated. The molecular genetic mechanism of this disease is not known. Several reports show the development of renal cell carcinoma in Tuberous sclerosis patients. TSC 1 or TSC 2 gene may be responsible for these tumors. The detail in this disease not well known. Molecular genetic analyses for hereditary renal cancer identified several oncogenes and tumor suppressor genes in hereditary as well as sporadic renal carcinomas. Future studies may reveal new category of oncogenes or tumor suppressor genes that are involved in the human kidney cancer development.

Amino Acid Sequence↗
PubMed1999

[Clinical statistics of stage I testicular tumor].

PURPOSE: A survey of stage I testicular tumors in the Chugoku-Shikoku district was taken in order to explore the clinical characteristics. PATIENTS AND METHODS: Three hundred and forty eight cases of stage I testicular tumor treated at 46 facilities in the Chugoku-Shikoku district between 1984 and 1992 were collected. Subjects' background factors, treatment methods and prognosis were studied. RESULTS: Tissue types were 249 (71.6%) seminoma and 99 (28.4%) non-seminoma. Adjuvant therapy for seminoma cases included 138 post-operative radiotherapy (4 recurrences, 3 cancer deaths), 57 chemotherapy (no recurrences, 2 contralateral testis tumor cases) and 48 were under surveillance (no recurrence). Adjuvant therapy for non-seminoma cases included 47 chemotherapy (1 recurrence) and retroperitoneal lymph node dissection was performed on 6 cases. Forty cases were under surveillance (1 recurrence). Of 8 (2.3%) cases with recurrence, 6 showed onset within two years and 2 after two years. Four of the 8 cases with recurrence were seminoma (1.1% of seminoma cases) and the other 4 were non-seminoma (4.0% of non-seminoma cases). All 3 (0.9% of all cases) of the cancer death cases were seminoma that received post-operative radiotherapy, while there were no cancer deaths in non-seminoma cases. CONCLUSION: Prognosis of stage I testicular tumor is good. Although the recurrence rate was higher in non-seminoma cases, cancer deaths were only observed in seminoma cases.

Adolescent↗
PubMed1998

High alkaline phosphatase activity in 3p-induced human renal cancer cells.

Recent studies have suggested that a tumor suppressor gene is located on the short arm of chromosome 3 (3p) for tumorigenesis of sporadic renal cell carcinoma. In this study, we introduced 3p from normal human fibroblasts into the renal cancer cell line YCR and this introduction clearly resulted in inhibited growth in vitro and in vivo. Furthermore, we investigated several enzyme activities of original YCR cells and 3p-induced clones (YCR-151 and YCR-152) and found that only alkaline phosphatase activity in 3p-induced clones was significantly increased compared to that of the original YCR cells.

Alkaline Phosphatase↗
PubMed1998

Overexpression of c-met proto-oncogene associated with chromophilic renal cell carcinoma with papillary growth.

Various genetic changes are involved in human renal cell carcinomas (RCCs). However, the molecular events related to other cytomorphological subtypes of RCC are not well known, apart from the relationship between the von Hippel-Lindau tumour suppressor gene and clear cell subtype RCC. We examined the overexpression of several growth factor receptors immunohistochemically and analyzed their relationship to the cytomorphological characters in 120 cases of RCCs. These receptors included c-met proto-oncogene product (c-MET), epidermal growth factor receptor (EGFR) and transforming growth factor beta receptor II (TGFbetaR). The overexpression of c-MET was detected in all cases (20/20) of the tubulo-papillary growth type and 78.3% (18/23) of chromophilic cell subtype, resulting in a very significant associations between c-MET overexpression and tubulo-papillary growth RCCs (P<0.0001), c-MET and chromophilic subtype RCCs (P<0.0001), and c-MET and EGFR (P<0.0001). EGFR overexpression was significantly associated with the compact growth RCCs (49/89, P<0.0001), clear cell subtype RCCs (P<0.005) and the overexpression of TGFbetaR (P<0.0001). These results strongly suggest a close correlation between the overexpression of c-MET and development of the chromophilic subtype of RCC with papillary growth pattern. EGFR expression is closely related to the pathogenesis of the clear cell subtype of RCC with compact growth pattern. The overexpression of c-MET, EGFR, and TGFbetaR may have roles that are individually significant in the morphogenesis of RCC.

Adult↗
PubMed1998

Prognostic significance of cyclin E and p53 protein overexpression in carcinoma of the renal pelvis and ureter.

Cyclin E gene alteration in the cell cycle plays an important role in carcinogenesis, while p53 protein affects different phase checkpoint pathways by activating p21WAF1/CIP1 in the normal cell cycle. We immunohistochemically examined the expression of cyclin E and p53 proteins in 121 patients with transitional cell carcinoma (TCC) of the renal pelvis and ureter to determine their significance for tumour behaviour and patient prognosis. Cyclin E and p53 immunostaining of the nucleus was observed in 36 tumours (29.8%) and 35 tumours (28.9%) respectively. A significant percentage, 69.4% (25 out of 36 tumours), of the cyclin E-positive tumours exhibited simultaneous labelling for p53 (P < 0.05). Mirror-section technique was performed in five selected double-positive tumours to identify cancer cells that were nuclei positive for both cyclin E and p53. The prevalence of cases simultaneously exhibiting both cyclin E and p53 immunostaining was higher in the high-grade tumours (P < 0.01) than in the other types of tumours. Patients with TCCs coexpressing cyclin E and p53 had a significantly poorer prognosis than those expressing neither cyclin E nor p53 (P < 0.001). These in vivo findings provide evidence for cyclin E protein overexpression in TCCs intimately associated with p53 alteration and suggest that simultaneous overexpression of both cyclin E and p53 is related to tumour behaviour and poor prognosis.

Aged↗