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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For transitional cell carcinoma of the bladder, clinical data indicate that invasive, metastatic tumors can arise through at least two different progression pathways. The majority of invasive, metastatic bladder neoplasms clinically present de novo, i.e., the patients have no history of malignant bladder disease. This implies that the highly malignant tumor cells either arise de novo or have undergone a rapid progression. Alternatively, a considerable fraction of patients with superficial bladder cancer process to invasive disease after a history of relatively benign superficial TCC. The molecular and cell biological basis of tumor progression is only poorly understood. Clearly, a better understanding of this progress could have profound clinical implications, since patients with superficial TCC with a high risk for progression would have to be treated more aggressively. We discuss the problems that are associated with tumor biological studies on early steps in the progression of TCC, especially from a "model system point of view."
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PMID:Critical review of the models to study the biologic progression of bladder cancer. 146 97

Forty transitional cell carcinomas of the human urinary bladder (TCCs) were examined for numerical aberrations of chromosomes 1, 7, 9, and 11 by in situ hybridization using chromosome-specific probes. Our interphase cytogenetic study of 24 low-grade, noninvasive TCCs, which were near-diploid by flow cytometry, showed a numerical aberration for at least 1 of these chromosomes in 14 of these cases. Most strikingly, a monosomy for chromosome 9 was found in 9 of 24 low-grade TCCs. A trisomy for chromosomes 1, 7, and 11 was detected in 5, 2, and 1 case(s), respectively. In 1 case a monosomy for chromosome 1 was detected by in situ hybridization. Monosomy for chromosome 9 was the only detected numerical change in 5 low-grade TCC cases. Examination of 16 invasive TCCs showed extra copies for chromosomes 1 and 7 in 7 flow cytometrically diploid cases with numerical chromosome aberrations; also, loss of chromosome 9 was detected. In 5 invasive and 2 noninvasive aneuploid/tetraploid TCCs a profound imbalance between the different chromosomes was found. In 5 of these cases an evident underrepresentation of chromosome 9 in comparison to chromosomes 1, 7, and 11 was detected. This underrepresentation of chromosome 9 in diploid, as well as aneuploid, TCCs, and in some cases the constant ratio between this chromosome and the other chromosomes, may be explained by a process of tetraploidization. Therefore, loss of chromosome 9 may be one of the primary genetic events in TCC oncogenesis, with secondary events, such as tetraploidization, correlated to tumor progression. Our results show that in situ hybridization can be routinely used to study important cytogenetic changes which occur during the development of a malignant disease.
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PMID:Numerical chromosome 1, 7, 9, and 11 aberrations in bladder cancer detected by in situ hybridization. 198 81

High grade superficial TCC of the bladder (T1 G3) has an important risk of recurrence and/or progression (40%) after TUR-B and a low survival rate (57% at 3 years, 50% at 10 years). Intravescical treatment with BCG seems to be able to reduce these rates. 64 patients with T1 G3 vescical TCC underwent a "second look" TUR-B. 9/64 patients presented locally advanced tumor (T2-3) or persistent high risk superficial TCC (T1 G3 + Tis) and underwent to early cistectomy. BCG intravescical therapy has been performed in the remaining 55 patients: 10 of them had not been evaluated because local or sistemic toxicity and consequent early interruption of treatment. BCG Pasteur was given weekly at the dose of 75 mg for two cycles of 6 weeks with a rest period of 6 weeks between the two cycles and then monthly for one year and every three months during next two years too. After the first 6 weeks 43/45 patients resulted tumor-free and 2/45 presented persistent Tis: after the second 6 weeks-cycle of BCG, two other patients had evidence of vescical TCC (one T2 G3 and the other T1 G3); all these four patients were submitted to radical cystectomy or radiotherapy. Of the reamining 41 patients, 28 presented had no recurrences, nowadays living and tumor-free; 3 presented local neoplastic progression and dead; relapsed in T1 G2 and are living NED after local chemotherapy. At a mean follow-up of 18 months, the total amount of recurrences is 17/45 (38%), progression rate is 4/45 (8.8%), exitus 5/45 (11%) and living NED are 28/45 (62%). In our opinion local BCG treatment for T1 G3 bladder cancer, after TUR--B, seems to be able to reduce the risk of recurrence and mortality.
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PMID:[Role of BCG in T1G3 bladder transitional cell carcinoma (TCC): our experience]. 866 24

Mutations of p53 gene have been found in a variety of human malignancies; however, the impact of immunohistological detection of p53 expression in the development and progression of TCC of the bladder is still uncertain. In the present study, we investigated the p53 oncoprotein expression and compared the findings to DNA ploidy and pathohistological stage and grade. The study included 147 patients with transitional cell carcinoma of the bladder investigated between February 1981 and September 1994. The average age of the 55 women and 92 men was 67 years (range: 20-71 years). A total of 76 patients (52%) had stage pTa to pT1, 35 (24%) stage pT2, 25 (17%) stage pT3, and 11 (7%) stage pT4 disease. Frozen sections of tumor biopsies obtained by transurethral resection were immunohistochemically stained using the monoclonal antibody clone D0-7 (DAKO), which recognized two different epitopes for mutant and wild-type p53 protein. Tumors expressing p53 in more than 10% of the tumor nuclei were regarded as positive. The DNA ploidy was determined by image analysis. Immunohistochemical detection of p53 expression was found in 84 (57%) of the 147 tumors examined. Positive p53 staining was seen in grade I tumors in 10 to 25%, in grade II tumors 25 to 75%, and in grade III up to 58% of the tumor nuclei. There was a positive correlation between p53 expression and pathological stage (28% in pTa, 73% in pT1-2, and 68% in pT3-4 tumors). There was no appreciable relationship between DNA Ploidy and p53. Although carcinomas with p53 expression had a slight tendency to be more prevalent among higher disease stages and poorly differentiated transitional cell carcinoma, immunohistochemical detection of p53 is not a valuable tool for predicting the outcome of patients with TCC or for identifying subgroups of patients that may be at a higher risk for tumor progression.
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PMID:Immunohistochemical detection of p53 protein in transitional cell carcinoma of the bladder in correlation to DNA ploidy and pathohistological stage and grade. 946 48

A new transitional cell carcinoma cell line, BCCA-1, derived from a primary urinary bladder carcinoma, was characterized with respect to the growth patterns of in vitro culture, xenotransplantability in SCID mice and immunophenotypic profile. The most unusual finding was a strong tendency of forming many aggregates (multicell spheroids) in the first few days of flask cultures, followed by the attachment of spheroids to monolayer fibroblasts, which came along from stroma of the same tumor. Unlike those reported tumor spheroids whose peripheral layers contained proliferative cells, BCCA-1 spheroids rarely contained mitotic cells. The three-dimensional architecture of BCCA-1 spheroids drastically changed by the attachment of spheroids to fibroblasts, from which epithelial tumor cells spread; this was accompanied by pseudopodia formation and highly aggressive growth of tumor cells. As the fibroblasts degenerated due to overgrowth, tumor cells started to aggregate by retracting their pseudopods and forming many semi-attached spheroids, which eventually detached from the sheet of degenerated fibroblasts. BCCA-1 produced solid tumors as xenografts in SCID mice by subcutaneous injection with as low as 5 x 10(6) cells, suggesting malignant nature of these cells. Immunostaining revealed the expression of MHC-class I, S100 protein, cytokeratin CK7 and CK20, beta-HCG, CEA, epithelial membrane antigen, Le(y) and folate-binding protein by this tumor. While the biological significance of spheroid formation of this kind by BCCA-1 cells remains unclear, it may represent a protection mechanism, by which TCC cells could sustain their viability under unfavorable culture conditions, but proliferate when the conditions became improved, such as the presence of fibroblasts. Our results point to the importance of tumor-associated stromal fibroblasts in TCC tumor progression. Further mechanistic studies to elucidate the mechanism involved in the stromal cell contact mediated-activation of TCC cells in this model system are warranted.
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PMID:Human bladder carcinoma cells with an unusual pattern of in vitro growth: transition from nonproliferative spheroids to active monolayer growth upon interaction with tumor-derived fibroblasts. 1081 Mar 50

We analyzed six cystectomized specimens diagnosed as transitional cell carcinoma by immunohistochemical evaluation to determine the presence of c-erbB2, transforming growth factor-alpha (TGF-alpha), c-myc, c-fos, and c-fms. Representative sections of flat lesions with atypia (e.g., reactive atypia, dysplasia, and carcinoma in situ) and invasive neoplasms (transitional cell carcinoma, TCC) were selected for each cystectomy specimen according to the new WHO/ISUP classification. The average percentage of cells found positive for c-erbB2 were 16.3%, 45.5%, 46.1% and 67.7% in the reactive atypia, dysplasia, carcinoma in situ, and invasive TCC, respectively. The average percentage of cells found positive for TGF-alpha were 9.7%, 13.3%, 13.5%, 30.3%, respectively. The cells were negative for the oncoproteins c-myc and c-fos. The average percentage of cells found positive for the oncoprotein c-fms was 10.6%, 15.5%, 16.7%, and 45.5% respectively. The results of this study indicated that various oncoproteins are expressed differently. c-erbB2, TGF-alpha and c-fms expression was gradually increased during tumorous progression of the urothelium from reactive atypia to invasive carcinoma. The presence of c-erbB2, TGF-alpha and c-fms is an important marker for detection of an early precursor lesions of invasive carcinoma. However, c-myc and c-fos were not expressed in the urothelial reactive atypia and dysplasia and did not correlate with tumor progression.
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PMID:Oncoprotein changes in the flat lesions with atypia and invasive neoplasms of the urinary bladder. 1129 84

The prostaglandin E2 receptor, EP4 receptor (EP4R), plays an important role in the development of transitional cell carcinoma of the upper urinary tract (TCC-UUT). However, the clinical significance of other EP receptors (EP1R-3R) is not clear. Furthermore, the pathological function of EP receptors in such patients is not understood. In the present study, we examined the expression of EP1R-3R in 101 TCC-UUT tissues by immunohistochemistry. Furthermore, we defined the relationship between cyclooxygenase (COX)-2 and EP receptor expression, proliferation index (PI), microvessel density (MVD), and expression of metalloproteinase-2 (MMP-2), urokinase-type plasminogen activator (uPA), and exon v6 containing CD44 isoform (CD44 v6) by multivariate analysis. The expression of EP1R, EP2R, and EP3R was positive in 20 (19.8%), 26 (25.7%), and 14 (13.9%) tumor samples, respectively. Expression of these receptors was not associated with pathological findings or survival. COX-2 and EP4R were independently associated with MVD and MMP-2, and uPA or PI and MMP-2, respectively. Other EP receptors were not influenced by any factors. Our results suggest that EP1R-3R play a minimal role in cancer progression in patients with TCC-UUT. On the other hand, EP4R regulates tumor progression via cancer cell proliferation and MMP-2, distinct from COX-2.
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PMID:Pathological function of prostaglandin E2 receptors in transitional cell carcinoma of the upper urinary tract. 1660 7

This study aimed to investigate the relationship of caveolin-1 expression with prognosis in patients with transitional cell carcinoma of the upper urinary tract (TCCUUT). Formalin-fixed, paraffin-embedded tissue sections of TCC-UUT from 98 patients, who had undergone radical nephroureterectomy, were stained immunohistochemically using antibodies against caveolin-1. The expression pattern of caveolin- 1 was compared with the clinicopathological variables. The caveolin-1 expression was significantly correlated with T stage (p<0.001) and grade (p=0.036). The survival rate of patients with caveolin-1 positive tumors was significantly lower than that of patients with caveolin-1 negative tumors (p<0.0001). The univariate analyses identified T stage, grade, and caveolin-1 expression as significant prognostic factors for cancer-specific survival, whereas the multivariate analyses indicated that T stage and caveolin-1 expression were independent prognostic factors. These results show that the increased expression of caveolin-1 is associated with tumor progression and poor prognosis in TCC-UUT, suggesting that caveolin-1 may play an important role in the progression of TCC-UUT.
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PMID:Impact of caveolin-1 expression on the prognosis of transitional cell carcinoma of the upper urinary tract. 1843 15

The expression of claudin-11 in benign and malignant bladder tissue and the effect of forced expression of claudin-11 on tight junction function and invasiveness of bladder cancer cells were studied. Claudin-11 expression was tested in bladder cancer cell lines (T24/83, RT 112/84 and EJ138) using reverse transcription-polymerase chain reaction (RT-PCR) and in benign and malignant bladder tissue by quantitative RT-PCR and immunohistochemistry. T24/83 cells were transfected with the pcDNA.1/NT-GFP-TOPO vector containing full-length human claudin-11 sequence. Stable-transfected cells overexpressing claudin-11 (T24Cl-11Ex), wild-type cells (T24WT) and the empty plasmid control clone (T24GFP) were compared using transurothelial resistance (TUR), in vitro adhesion, invasion and growth assays. Claudin-11 was strongly expressed in the non-invasive RT112/84 cell line compared to the invasive T24/83 and EJ138 TCC cell lines. Benign bladder tissue demonstrated equal expression of claudin-11 mRNA as carcinoma, but displayed more intense staining than malignant tissue on immunohistochemistry. Forced-expression of claudin-11 in T24/83 cells was confirmed by PCR, immunoprecipitation and by immunofluorescence, which demonstrated increased perinuclear claudin-11 staining. Forced expression of claudin-11 did not affect TUR (p = 0.243), but significantly reduced invasion (p = 0.001) while increasing cell matrix adhesion (p = 0.001) and growth rates (p = 0.001). The greater expression of claudin-11 in benign vs. malignant tissue and non-invasive vs. invasive cell lines, and its effect in reducing bladder cancer cell invasiveness suggests that claudin-11 may have a role in preventing cancer progression and may serve as a therapeutic target in reducing metastasis.
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PMID:Claudin-11 decreases the invasiveness of bladder cancer cells. 2146 49

Androgen receptor (AR) signals play important roles in bladder carcinogenesis and tumor progression. Activation of the epidermal growth factor receptor (EGFR) family, including EGFR and ERBB2, leads to bladder cancer cell growth and correlates with poor patients' prognosis. However, cross talk between AR and EGFR/ERBB2 pathways in bladder cancer remains poorly understood. In AR-positive bladder cancer UMUC3 and TCC-SUP cells, dihydrotestosterone (DHT) increased the expression of EGFR and ERBB2 both in mRNA and in protein levels, and an anti-androgen hydroxyflutamide antagonized the effect of DHT. The necessity of AR was confirmed by silencing the receptor, using short hairpin RNA (shRNA), in UMUC3 cells, as well as by expressing the receptor in AR-negative 5637 cells. Of note were much higher basal levels of EGFR and ERBB2 in UMUC3-control-shRNA than in UMUC3-AR-shRNA and those of EGFR in 5637-AR than in 5637-V. DHT additionally upregulated the levels of phosphorylation of EGFR (pEGFR) and its downstream proteins AKT (pAKT) and ERK1/2 (pERK), induced by EGF treatment, in AR-positive cells. Immunohistochemistry on cystectomy specimens showed strong associations between expressions of AR and EGFR (P=0.0136), pEGFR (P=0.0041), ERBB2 (P=0.0331), or pERK (P=0.0274), but not of pAKT (P=0.5555). The Kaplan-Meier and log-rank tests further revealed that positivity of AR (P=0.0005), EGFR (P=0.2425), pEGFR (P=0.1579), ERBB2 (P=0.2997), or pERK (P=0.1270) and negativity of pAKT (P=0.0483) were associated with tumor progression. Our results indicate that AR activation upregulates the expression of EGFR and ERBB2 in bladder cancer cells. AR signals may thus contribute to the progression of bladder cancer via regulation of the EGFR/ERBB2 pathways.
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PMID:Dihydrotestosterone upregulates the expression of epidermal growth factor receptor and ERBB2 in androgen receptor-positive bladder cancer cells. 2161 11


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