Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007138 (transitional cell carcinoma)
 3,949 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of multidrug resistant proteins in bladder cancer and clinical implication was studied. Expression of multidrug-associated protein (MRP), P-glycoprotein (P-gp), P53 and Bcl-2 proteins were detected by using immunohistochemical method in 40 specimens of bladder transitional cell carcinoma. The results showed that the positive rate of MRP, P-gp, P53 and Bcl-2 was 52.5%, 57.5%, 47.5% and 62.5% respectively. The positive rate of MRP, P-gp, P53 and Bcl-2 in the grade I, II and III of tumors was 46.3%, 38.5%, 38.5%, 23.1%; 52.9%, 39.8%, 47.1%, 76.4%; 60.0%, 80.0%, 60.0%, 90.0% respectively. The positive rate of MRP, P-gp, P53 and Bcl-2 in 24 primary tumor specimens was 37.5%, 41.7%, 33.3%, 45.8% and that in 16 cases in recurrent specimens receiving chemotherapy 75.0%, 81.3%, 68.8%, 87.5% respectively. It was suggested the positive rate of MRP, P-gp, P53 and Bcl-2 was increased with the advance of tumor grade. The positive rate of four proteins in all recurrent cases was significantly increased (P < 0.05). The expression of MRP, P-gp, P53 and Bcl-2 proteins might be the important factors for chemotherapy failure.
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PMID:Expression of multidrug-associated protein, P-glycoprotein, P53 and Bcl-2 proteins in bladder cancer and clinical implication. 1152 49

Several in vitro studies have shown that nitric oxide (NO) produced by NO synthase (NOS), such as inducible NOS (iNOS) play an important role in tumor biology. We immunohistochemically examined the expression of iNOS and p53 proteins in patients with transitional cell carcinoma (TCC) of the urinary tract, including adjacent dysplastic lesions to determine the significance of the tumor behavior. Of total 94 tumors, in the present study, 41 (43.6%) tumors exhibited homogeneous immunostaining (diffuse strong positivity in tumor cells, >60%) and 53 (56.4%) tumors heterogeneous staining (variable positivity in tumor cells, 20-60%). No TCCs exhibited negative iNOS immunostaining was found. Thirty (31.9%) of 94 TCCs were positive with anti-p53 antibody, including 23 of homogeneous and 7 of heterogeneous staining. Of 23 TCCs with homogeneous p53 immunostaining, 11 tumors exhibited homogeneous iNOS immunoreaction. In the present study, dysplastic lesions adjacent to carcinomas were detected in 64 cases including 36 TCCs with homogeneous iNOS expression. All dysplastic lesions adjacent to the 36 TCCs with homogeneous iNOS immunostaining exhibited homogeneous iNOS immunostaining. No significant association between iNOS immunoreactivity and any clinicopathological factors as well as p53 immuno-reactivity were found. These in vivo findings provide evidence for frequent iNOS protein expression in TCC. In addition, our observations indicate that overexpression of iNOS expression may be one of the early events in the carcinogenesis of TCC.
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PMID:Immunohistochemical findings of nitric oxide synthase expression in urothelial transitional cell carcinoma including dysplasia. 1160 48

The aim of this study was to examine any relation between DNA ploidy and previously detected TP53 (p53) or p21WAF1/CIP1 expression in 94 patients with muscle-invasive transitional cell carcinoma of the urinary bladder and to associate these factors with survival. DNA ploidy was determined by image cytometry. In a subgroup of patients, the mutational status of the TP53 gene was assessed by temporal temperature gradient electrophoresis (TTGE) or perpendicular denaturant gradient gel electrophoresis (DGGE) and subsequent sequencing. Significantly more aneuploid than euploid tumours showed TP53 accumulation (p = 0.003). Patients with aneuploid tumours lived longer than patients with euploid tumours (p = 0.003). In the euploid, but not in the aneuploid group, TP53 and p21WAF1/CIP1 were associated with cancer-specific survival (p = 0.002 and 0.02, respectively). Patients with > 50% TP53 expression had the longest survival time. Mutation analyses showed acceptable concordance with TP53 expression. We conclude that DNA aneuploidy may confer increased radiosensitivity in bladder cancer patients and that TP53 accumulation may confer increased radiosensitivity, but its effect is detectable only in euploid tumours.
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PMID:TP53 and p21WAF1/CIP1 behave differently in euploid versus aneuploid bladder tumours treated with radiotherapy. 1166 39

The effect of the tumor suppressor gene TP53 on repair of genomic DNA damage was examined in human urinary bladder transitional cell carcinoma (TCC) cell lines. Utilizing TCC10 containing wild-type p53 (wt-p53) as the parental line, an isogenic set of cell lines was derived by retroviral infection that expressed a transdominant mutant p53 (Arg --> His at codon 273, TDM273-TCC10), or the human papilloma virus 16-E6 oncoprotein (E6-TCC10). 32P-postlabeling analyses were performed on DNA from TCC cultures obtained after treatment with N-hydroxy-4-aminobiphenyl (N-OH-ABP), N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP) and N-acetoxy-4-acetylaminobiphenyl (N-OAc-AABP). The major adduct was identified as N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP) with all three chemicals. The amount of adducts in urothelial DNA ranged between 0.1 and 20 per 10(6) nucleotides, N-OAc-AABP yielding the highest levels, followed by N-OH-ABP and N-OH-AABP. To determine, if the functional status of p53 affects the rate of repair of dG-C8-ABP in genomic DNA, TCC10 and the TDM273-TCC10 and E6-TCC10 isotypes were exposed to N-OH-AABP for 12h and the DNA damage was allowed to repair up to 24h. The adduct levels were quantified and compared between the TCC10 isotypes. The amounts of dG-C8-ABP that remained in genomic DNA from E6-TCC10 and TDM273-TCC10 were approximately two-fold higher, as compared to the parental TCC10. At the dose used for DNA repair studies, N-OH-AABP or N-OAc-AABP did not induce apoptosis in TCC10. However, N-OAc-AABP at high doses (>5 microM) induced apoptosis, as evidenced by DNA fragmentation analyses. Furthermore, N-OAc-AABP-mediated apoptosis was independent of the functional status of wt-p53, since both E6-TCC10 and the parental TCC10 exhibited DNA fragmentation following treatment. These results suggest that p53 might modulate the repair of DNA adducts generated from the human bladder carcinogen ABP in its target human uroepithelial cells. This implies that in p53 null cells the unrepaired DNA damage could cause accumulation of mutation, which might contribute to increased genomic instability and neoplastic progression.
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PMID:Human urinary bladder epithelial cells lacking wild-type p53 function are deficient in the repair of 4-aminobiphenyl-DNA adducts in genomic DNA. 1180 9

We present a rare case of advanced bladder cancer in a young female. A 27-year-old woman had the chief complaint of proteinuria. A clinical examination revealed a papillary, broad-based bladder tumor with a clinical stage of T3, N3, M0. Preoperatively, 3 courses of neoadjuvant chemotherapy with methotrexate, adriamycin, and cisplatin were performed, and proved to be effective. Radical cystectomy was done and the histopathologically it was diagnosis as Grade 2 transitional cell carcinoma, which did not show any p53 gene mutation. The patient's postoperative clinical course was uneventful, and she remained disease free for 27 months. Bladder carcinoma in patients under 30 years of age tends to have a early stage and a low grade. However, the above described 27-year-old female patient demonstrated the advanced stage bladder tumor. Therefore, it should be kept in mind to accurately evaluate young patients with transitional cell carcinoma of the bladder and not to rule out the possibility of advanced disease even though a patient is young.
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PMID:Advanced bladder cancer in a young female: a case report. 1180 41

We investigated the prognostic and predictive relevance of p53, MDM2, and bcl-2 protein expression in patients with transitional cell carcinoma (TCC) of the bladder. The expression of p53, MDM2 and bcl-2 protein was studied by immunohistochemical methods in paraffin-embedded specimens from 119 patients whose clinicopathologic data confirmed TCC of the bladder. Multivariate analyses of prognostic factors were performed, and correlations with classical clinicopathologic parameters were examined. Sixty-one, 12, and 17% of cases were considered positive for expression of p53, MDM2 and bcl-2, respectively. p53 expression correlated with stage (p=0.0209), but not MDM2 and bcl-2 with any clinicopathologic parameters. In Cox's regression analysis, staging demonstrated a statistically worse prognosis (hazard ratio 1.636; p=0.0059) while bcl-2 (hazard ratio 0.179; p=0.0474) expression showed favorable prognosis in stage T2-4 invasive TCC of the bladder. Co-expression with p53/MDM2 (hazard ratio 0.367; p=0.0401) and p53/bcl-2 (hazard ratio 3.487; p=0.0111) overexpression were associated with favorable and unfavorable prognosis in stage T2-4 invasive TCC of the bladder, respectively. Our results indicate that staging is the most useful parameter to predict clinical outcome in patients with TCC of the bladder. Determinations of bcl-2 and co-expression p53/MDM2 and p53/bcl-2 may be useful for predicting tumor behavior and prognosis in stage T2-4 invasive type TCC of the bladder.
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PMID:Clinical significance of p53, MDM2 and bcl-2 expression in transitional cell carcinoma of the bladder. 1183 89

Bladder cancers are classified as: transitional cell carcinoma (TCC), the most frequent in Europe/USA, squamous cell carcinoma (SCC), more frequent in the Middle East and in Africa, adenocarcinoma and small cell carcinoma, rare. TCC exhibit pseudo diploid karyotypes with only a few anomalies in early stages, evolving towards pseudo-tetraploides complexes karyotypes. Partial or complete monosomy 9 (-9) is an early event, found in half cases. Deletion (11p) or -11 is found in 20-50% of cases, more often in high grade and invasive tumours. Del(13q) is found in 25% of cases and correlated with high grade/stage; tumours with Rb alterations are invasives. Del(17p) is a late event, found in 40% of cases; P53 alterations are correlated with grade and stage, tumour progression, and a worse prognosis. Del(1p), i(5q), +7, and many other rearrangements - more often deletions than duplications - are frequently found. These losses of heterozygocity point to a multistep complex process involving tumor suppressor genes. In SCC, monosomy 9 is also an early event, even more frequent than in TCC; homozygous deletion of P16 is frequent. Trisomy 7 seems to be more frequent than in TCC. Chromosome 17 is often implicated, especially in high grades/stages; the profile of mutations of P53 is different from what is found in TCC. Allelic losses of 3p, 8p, 9p, 9q, 17p are frequent. The karyotype is more complex in advanced grades/stages, as in TCC.
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PMID:[From cytogenetics to cytogenomics of bladder cancers]. 1188 56

We evaluated 71 muscle-invasive transitional cell carcinomas (TCCs) of the bladder by tumor compartments. Kinetic parameters included mitotic figure counting, Ki-67 index, proliferation rate (DNA slide cytometry), and apoptotic index (in situ end labeling [ISEL] of fragmented DNA using digoxigenin-labeled deoxyuridine triphosphate and Escherichia coli DNA polymerase [Klenow fragment]). At least 50 high-power fields per compartment were screened from the same tumor areas; results are expressed as percentage of positive neoplastic cells. Mean and SD were compared by tumor compartment. DNA was extracted from microdissected samples (superficial and deep) and used for microsatellite analysis of TP53 and NF1 by polymerase chain reaction-denaturing gradient gel electrophoresis. Significantly higher marker scores were revealed in the superficial compartment than in the deep compartment. An ISEL index of less than 1% was revealed in 63% (45/71) of superficial compartments and 86% (61/71) of deep compartments. Isolated NF1 alterations were observed mainly in superficial compartments, whereas isolated TP53 abnormalities were present in deep compartments. Lower proliferation and down-regulation of apoptosis define kinetically the deep compartment of muscle-invasive TCC of the bladder and correlate with the topographic heterogeneity, NF1-defective in superficial compartments and TP53-defective in deep compartments.
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PMID:Kinetic profiles by topographic compartments in muscle-invasive transitional cell carcinomas of the bladder: role of TP53 and NF1 genes. 1210 62

In this study prognostic significance and clinical value of mutant p53 gene in bladder transitional cell tumors is investigated. In our clinic, between 1997-2000, transurethral resection was performed in 48 cases, 3 females (6%) and 45 males (94%) with the diagnosis of primary bladder tumor, age ranges between 30-81 years old (average 58.9 +/- 9.9). The patients whose pathology results were transitional cell carcinoma were gathered into two groups as p53 positive and p53 negative by immunohistochemical study. These cases who were followed 1-36 months were compared to each other for pathologic state, tumor grade, recurrence and survival. It's found out that mutant p53 accumulation is related to high grade and pathologic stage tumors. But it's concluded that p53 positivity doesn't effect recurrence and survival rates.
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PMID:The relation of mutant p53 accumulation in transitional cell carcinoma of bladder with pathological stage, grade, recurrence and survival. 1223 Feb 75

The members of the IAP (inhibitors of apoptosis) family, which includes survivin, have recently emerged as modulators of an evolutionarily conserved step in apoptosis. Survivin is present during embryonic and fetal development, but it is downregulated in normal adult tissues. However, it becomes re-expressed in a variety of cancers. We investigated the prognostic importance of the expression of survivin in transitional cell carcinoma of the upper urinary tract (TCC-UUT). In 126 cases of TCC-UUT, we examined its expression (using immunohistochemistry), and also its relationship with the expressions of bcl-2 oncoprotein, p53 oncoprotein, and proliferating cell nuclear antigen (PCNA) immunoreactivity, clinicopathologic parameters, and clinical outcome. A positive expression of survivin was recognized in 12.7% of samples, a granular pattern being apparent within the cytoplasm of tumor cells. Survivin expression did not correlate with clinicopathologic findings, bcl-2 oncoprotein expression, p53 oncoprotein expression, PCNA index, or prognosis. In the normal urothelium, its expression was not detected. In conclusion, the expression of survivin does not predict prognosis in TCC-UUT.
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PMID:Expression of survivin does not predict survival in patients with transitional cell carcinoma of the upper urinary tract. 1246 12


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