Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0005684 (bladder cancer)
 16,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dietary uracil at the 3% level induces urinary bladder tumors in rats through urolithiasis-dependent mechanical irritation. In the present study, comparison of lesions induced by uracil administration over the different periods of 36 weeks (middle-term) and up to 103 weeks (long-term) revealed significant elevation of both incidences and multiplicity of transitional cell carcinomas (TCCs) in the long-term group. Histopathological assessment in terms of tumor biology further demonstrated significantly higher grading on the basis of the degree of cellular and structural atypia, and greater depth of invasion in the long-term group. Application of markers for cell proliferation activities including proliferating cell nuclear antigen (PCNA) and silver-binding nucleolar organizer regions (AgNORs) also revealed significantly elevated AgNOR counts in the long-term group TCC. AgNOR counts and PCNA rates in TCCs showed relation to the histological grades. Thus the present study demonstrated that prolonged uracil-induced urolithiasis causes more biologically aggressive bladder carcinomas with invasive potential. Continuous stimulation of cell proliferation presumably has the potential to facilitate multiple genetic alterations leading to development of more malignant carcinomas. However, it should be borne in mind that the difference in bladder cancer development might also be related to the fact that the animals survived longer and that the early lesions therefore had more time to progress to more advanced stages.
 ...
PMID:Progressive growth of rat bladder carcinomas after exposure to prolonged uracil-induced urolithiasis. 799 27

It is important to know the proliferating ability and the malignant potential of each tumor. We studied 56 cases of pTa to pT1 superficial bladder tumors using immunohistochemical staining for proliferating cell nuclear antigen (PCNA), and compared the results with the clinical course of each patient. We obtained the following results. 1) We detected the PCNA positive nuclei in all cases, and the PCNA positive rates varied within a range of 1.1-77.5% with a mean of 34.0%. 2) The PCNA positive rate showed no correlation with age, sex, duration of paraffin-embedded, or pathological stage, but showed a significant correlation with the number of tumors, pathological grade of malignancy, or non-recurrence rate. PCNA positive rate of Grade 1 cases (n = 19, 15.6%: mean) was significantly lower than those of Grade 2 cases (n = 27, 39.9%) or Grade 3 cases (n = 10, 53.1%) (P < 0.01). The recurrence rate of the cases with PCNA positive rates of more than 34% (n = 24) was significantly higher than that of the cases with a PCNA positive rate of less than 34% (n = 32) (P < 0.05). In conclusion, the method of counting the rate of PCNA positive nuclei is considered to be very useful because of its applicability to paraffin-embedded tissue sections and the simple and rapid techniques. Our results in bladder cancer tissues suggest that this method may also be useful for investigating the proliferating ability and the malignant potential of tumors in general.
 ...
PMID:[Expression of proliferating cell nuclear antigen in superficial bladder cancer--application to paraffin-embedded tissue sections]. 809 49

The chemopreventive effects of indomethacin (IM) on the enhancement of bladder carcinogenesis and transitional-epithelial-cell proliferation by butylated hydroxyanisole (BHA) or sodium L-ascorbate (Na-AsA) were investigated. All animals were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 4 weeks. They then received 2% BHA or 5% Na-AsA for 20 weeks, followed by 20 ppm IM in the drinking water or normal tap water without supplement for a further 20 weeks, or BHA or Na-AsA alone or concomitantly with IM for 40 weeks. No differences in bladder-tumor development were found when IM was administered after cessation of BHA or Na-AsA exposure. However, IM in combination with either BHA or Na-AsA significantly reduced both the incidence and the multiplicity of papillomas and carcinomas as compared with the values of groups receiving BHA or Na-AsA alone. This was associated with decreased DNA synthesis and prostaglandin (PG) E2 levels in the existing bladder tumors. Combined treatment with IM did not exert any effects on BHA forestomach carcinogenesis. A separate 8-week combination study demonstrated that IM diminished the increase in expression of proliferation nuclear-cell antigen (PCNA) induced by BHA or Na-AsA alone. The present results suggest that PGE2 may be involved in promotion of rat bladder carcinogenesis and that the PG synthesis blocker IM might exert preventive effects on the development of bladder cancer in humans.
 ...
PMID:Chemoprevention by indomethacin of tumor promotion in a rat urinary bladder carcinogenesis model. 825 19

Overexpression of the TP53 gene protein detected by immunohistochemistry appears to identify those patients with superficial bladder cancer at risk of the development of muscle invasive or metastatic disease. However, the role of p53 overexpression in patients with advanced or metastatic bladder cancer is not yet well established. In the present study, 44 specimens from 44 patients with advanced stage bladder tumours (T2-T4) undergoing radical cystectomy were investigated for different biological and clinical characteristics as possible prognostic factors: sex, age, depth of tumour infiltration, T-stage, histological grade, lymph node status, application of adjuvant systemic chemotherapy (MVAC), proliferative activity (staining for proliferating cell nuclear antigen (PCNA) by monoclonal antibody (PC10) as well as overexpression of the p53 oncoprotein (monoclonal antibody pAb 1801)). After a median follow-up of 22 months, 16 of the 23 patients (70%) with more than 40% of tumour cells stained positively for p53 (Group B) died from tumour progression compared with 7 of the 21 patients (33%) with less than 40% of tumour cells positive for p53. During univariate analysis, p53 overexpression (P = 0.008), staining for PCNA (> or = 80% of cells positive) (P = 0.01) and tumour stage (P = 0.01) were significant prognostic factors for survival, among which p53 overexpression (P = 0.023) as well as T-stage (P = 0.012) remained independent significant predictors during multivariate analysis. Prospective studies are needed to confirm the independent prognostic potential of p53 overexpression in patients with advanced bladder cancer. The availability of more refined prognostic factors should assist decision making regarding the value of more aggressive treatment options, such as adjuvant or neoadjuvant chemotherapy, for prognostically defined subgroups of patients.
 ...
PMID:p53 overexpression as a prognostic factor for advanced stage bladder cancer. 865 50

Forty-eight patients with transitional cell carcinima (TCC) of the bladder were investigated. Routine paraffin-embedded sections were stained with proliferating cell nuclear antigen (PCNA) monoclonal antibody in order to determine the growth fraction of the bladder tumors and to correlate this with tumor grade, stage, development of recurrence and survival rate during follow-up. PCNA positive staining was detected in 95.8% (46/48) of the tumors. The mean labeling index (LI) of superficial tumors (Ta-1, n = 28) was 12.58 +/- 12.33%, and 34.55 +/- 21.89% in invasive tumors (T2-4, n = 18). A similar correlation was found in association with tumor grade. The patients were followed up for a mean of 4.9 years (range 1-14 years). The mean PCNA LI in nonrecurrent (n = 21) and simple recurrent (n = 7) superficial tumors was 11.29 +/- 11.79% and 16.44 +/- 14.05%, respectively, the difference not being statistically significant. To access survival, tumors with a PCNA LI above and below the median level (21%) were compared. Those patients (n = 19) with an index of > 21% (the mean of all the PCNA values) had a worse prognosis than those (n = 27) with an index of < 21%, a difference which is statistically significant. These results suggest that PCNA LI in bladder cancer may prove to be an objective and quantitative assay of biological aggressiveness and provide significant prognostic information, although it does not help the selection of patients at risk of simple recurrence in superficial tumors.
 ...
PMID:Expression and prognostic value of proliferating cell nuclear antigen in transitional cell carcinoma of the urinary bladder. 907 42

Immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and cathepsin D was performed on 60 transitional cell carcinoma (TCC) specimens from 60 patients with bladder cancer. The percentage of PCNA-positive cells (PCNA-labelling index) was determined by counting 500 or 1,000 cells, and cathepsin D expression was graded according to the extent of immunoreactivity to anti-cathepsin D antibody. The PCNA-labelling index was significantly higher in high-grade and high-stage tumors compared to that in low-grade and low-stage tumors. Cathepsin D was highly positive in grade-1 tumors. In contrast, 82% of grade-3 tumors and 76% of advanced tumors showed negative or low reactivity to anti-cathepsin D. Groups of high PCNA-labelling index and negative cathepsin D had significantly poorer prognoses compared to those of the low PCNA group and cathepsin D highly positive group, respectively, in univariate analyses. However, neither of these two factors were independent prognostic factors in multivariate analyses. These results suggest that the PCNA-labelling index and cathepsin D expression may indicate the malignant potential of TCC and may be able to provide additional information for predicting survival when stratifying for grade of bladder cancer.
 ...
PMID:Immunohistochemical studies of proliferating cell nuclear antigen and cathepsin D in transitional cell carcinoma of the urinary bladder. 939 54

To determine the relationship between PCNA expression and pathological stage, cellular grade, recurrence and prognosis of renal pelvic and ureteral cancer, research on PCNA proliferating index in 47 cases of renal pelvic and ureteral cancer we studied by immunohistochemistry S-P method. PCNA proliferating index of renal pelvic and ureteral cancer increased with pathologic stage and cellular grade. PCNA proliferating index of T3 + T4 was significantly higher than that of T1 + T2 (P < 0.01). PCNA proliferating index of G3 was significantly higher than that of G1 + G2 (P < 0.001). Those with higher PCNA proliferating index (III + IV) had higher bladder cancer recurrent rate after operation (60%, 12/20), those with lower PCNA proliferating index (I + II) had lower bladder cancer recurrent rate (22.2%, 6/27). P < 0.01. 35% (7/20) of those with III + IV PCNA proliferating index had simultaneous polyorganic urothalial cancer, 7.4% (2/27) of those with I + II PCNA proliferating index had simultaneous polyorganic urothelial cancer, P < 0.05. 7.4% (2/27) of those with I + II PCNA proliferating index had local recurrence and metastasis after operation, 40% (8/20) of those with III + IV had local recurrence and metastasis, P < 0.05. The 5-year survival rate of I + II was 86.7%, the 5-year survival rated of III + IV was 35.7% (5/14), P < 0.05. The findings suggest that PCNA proliferating index connects with pathological stage and cellular grade of renal pelvic and ureteral cancer. It is an important characteristic of low differentiation, invasiveness and simultaneous or sequentially polyorganic urothelial cancer. It may be an important prognostic indicator of renal pelvic and ureteral cancer.
 ...
PMID:[Expression and clinical significance of PCNA in renal pelvic and ureteral cancer]. 959 Jul 38

Bacillus Calmette-Guerin (BCG) immunotherapy for superficial bladder cancer is now widespread, but non-effective cases are not uncommon and it has yet to be clarified why this is the case. In an attempt to cast light on this problem, we evaluated differences between effective and non-effective cases immunohistochemically using p53, proliferating cell nuclear antigen (PCNA), and bcl-2 antibodies. Between March 1988 and March 1996 a total of 79 superficial bladder cancer patients were treated with BCG intravesical instillation therapy after transurethral resection of bladder tumor (TUR-Bt). Of these, 19 demonstrated recurrence after the initial treatment. From the 60 remaining patients without recurrence, we randomly chose 19 additional cases and evaluated both series for p53, PCNA and bcl-2 immunohistochemical staining using formalin-fixed, paraffin-embedded tissues. For the recurrent cases, material taken prior and subsequent to BCG therapy was available for 17 of the 19 patients. Positive staining for p53 was noted for 42.1% (8/19) of both recurrent and non-recurrent cases, without any difference between the two. The rates for PCNA and bcl-2 were 52.6% (10/19) and 47.4% (9/19) in recurrent, and 36.8% (7/19) and 78.9% (15/19) in non-recurrent cases, respectively. Thus, there was a significant difference for lower incidences of bcl-2 in recurrent cases (P = 0.044). Values for p53 and bcl-2 were respectively 47.1% (8/17) and 41.2% (7/17) pre-treatment, and 52.9% (9/17) and 35.3% (6/17) post-treatment in the recurrence group. In contrast to the similarity in these results, PCNA positive cases were 52.9% (9/17) pre-treatment and 17.6% (3/17) post-treatment. These data suggest that there are differences between BCG-sensitive and BCG-resistant bladder cancers in terms of bcl-2 expression.
 ...
PMID:Immunohistochemical evaluation of p53, proliferating cell nuclear antigen (PCNA) and bcl-2 expression during bacillus Calmette-Guerin (BCG) intravesical instillation therapy for superficial bladder cancers. 969 96

Soy isoflavones exhibit a number of biological effects, suggesting that they may have a role in cancer prevention. Our objectives are to determine whether components of soy products or purified soy isoflavones can inhibit the progression of bladder cancer. We compared the in vitro effects of pure soy isoflavones and soy phytochemical concentrate on growth curves, cell cycle progression, and apoptosis in murine and human bladder cancer cell lines. Pure soy isoflavones (genistein, genistin, daidzein, and biochanin A) and soy phytochemical concentrate exhibit dose-dependent growth inhibition of murine (MB49 and MBT-2) and human (HT-1376, UM-UC-3, RT-4, J82, and TCCSUP) bladder cancer cell lines, although the degree of inhibition varies among lines. Soy isoflavones induce a G2-M cell cycle arrest in all human and murine lines evaluated by flow cytometry. In addition, some bladder cancer lines show DNA fragmentation consistent with apoptosis. We next evaluated the ability of genistein, soy phytochemical concentrate, and soy protein isolate, respectively, to inhibit the growth of transplantable murine bladder cancer in vivo. C57BL/6 mice were randomly assigned to treatment groups (n = 12/group): (a) AIN-76A diet; (b) AIN-76A diet plus genistein, i.p., 50 mg/kg body weight/day; (c) AIN-76 diet with soy phytochemical concentrate at 0.2% of the diet; (d) AIN-76 diet with soy phytochemical concentrate at 1.0% of the diet; and (e) AIN-76A diet with soy protein isolate, 20% by weight. Mice were inoculated s.c. with 5 x 10(4) syngeneic MB49 bladder carcinoma cells, and tumor growth was quantitated. Neither genistein nor soy products reduced body weight gain. Tumor volumes from mice treated with genistein, dietary soy phytochemical concentrate at 1%, or dietary soy protein isolate were reduced by 40% (P < 0.007), 48% (P < 0.001), or 37% (P < 0.01), respectively, compared with controls. We characterized the effects of treatment on several biomarkers in tumor tissue: proliferation index by proliferating cell nuclear antigen staining, apoptotic index by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling staining, and angiogenesis by microvessel quantitation. Soy products reduced angiogenesis, increased apoptosis, and slightly reduced proliferation while showing no histopathological effects on the normal bladder mucosa. Our data suggest that soy isoflavones can inhibit bladder tumor growth through a combination of direct effects on tumor cells and indirect effects on the tumor neovasculature. Soy products warrant further investigation in bladder cancer prevention and treatment programs or as antiangiogenic agents.
 ...
PMID:Inhibition of murine bladder tumorigenesis by soy isoflavones via alterations in the cell cycle, apoptosis, and angiogenesis. 982 37

During the 11-year period subsequent to the Chernobyl accident, the incidence of urinary bladder cancer in Ukraine has increased from 26.2 to 36.1 per 100,000 population. Cesium-137 (137Cs) accounts for 80-90% of the incorporated radioactivity in this population, which has been exposed to long-term, low-dose ionizing radiation, and 80% of the more labile pool of cesium is excreted via the urine. The present study was performed to evaluate the histopathological features and the immunohistochemical status of p53, p21WAF1/Cip1, cyclin D1 and PCNA (proliferating cell nuclear antigen) in urinary bladder mucosa of 55 males (49-92 years old) with benign prostatic hyperplasia who underwent surgery in Kiev, Ukraine, in 1995 and 1996. Group I (28 patients) inhabiting radiocontaminated areas of the country, group II (17 patients) from Kiev city with less radiocontamination and a control group III (10 patients) living in so-called "clean" areas of Ukraine were compared. In groups I and II, an increase in multiple areas of moderate or severe dysplasia or carcinoma in situ was seen in 42 (93%) of 45 cases. In addition, two small transitional cell carcinomas were found in one patient in each of groups I and II. Nuclear accumulation of p53, PCNA, cyclin D1, and to a lesser extent p21WAF1/Cip1, was significantly increased in both groups I and II as compared with the control group III, indicating possible transformation events or enhancement of repair activities, that may precede the defect in the regulatory pathway itself, at least in the G1 phase of the cell cycle. Our results suggest that early malignant transformation is taking place in the bladder urothelium of people in the radiocontaminated areas of Ukraine and that this could possibly lead sometime in the future to an increased incidence of urinary bladder cancer.
 ...
PMID:Urinary bladder lesions after the Chernobyl accident: immunohistochemical assessment of p53, proliferating cell nuclear antigen, cyclin D1 and p21WAF1/Cip1. 1018 84


<< Previous 1 2 3 4 5 6 7 Next >>