Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between 1986 and 1989, 14 patients undergoing cystectomy for bladder cancer, in pathological stage high risk pT2 group, pT3-4 and/or with N+ disease, received postoperative adjuvant methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) chemotherapy. Of the 14 patients 10 were alive with no evidence of disease for an average of 41 months. Tumor recurrence was seen in 4 patients (bone in 2, lungs in 1, brain in 1 patient). Of the 4 patients, 3 patients died of cancer progression at an average of 26 months and 1 patient was alive with tumor for 30 months. Their actual survival rate at 64 months was 70%, which was significantly higher than that of the historical control groups (1974-1981: 18%, 1982-1985: 46%). Although postoperative adjuvant M-VAC chemotherapy for invasive bladder cancer seemed effective in this study, a controlled randomized study will be necessary to conclude if it could be of real benefit for these patients.
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PMID:[Postoperative adjuvant M-VAC chemotherapy for invasive bladder cancer]. 160 58

From June 1982 through December 1985, 25 patients who had undergone radical cystectomy with pelvic node dissection for pathologic stage-pT3 or -pT4 and/or N+ disease received adjuvant chemotherapy involving the injection of cis-platinum alone or in combination with adriamycin and 5-fluorouracil (CAF). Thirteen patients also received preoperative adjuvant chemotherapy involving the infusion of cis-platinum, adriamycin, and mitomycin C into the bilateral internal iliac arteries. Postoperative adjuvant chemotherapy was performed using the following two protocols. Protocol 1 (18 cases) consisted of cis-platinum alone being administered every week for 3 weeks and then every month for 1 year. In protocol 2 (7 cases), cisplatinum, adriamycin, and 5-fluorouracil were administered at 3-week intervals on three occasions and then every month for 1 year. Eighteen patients were still alive with no evidence of disease after an average of 26 months. One patient died as a result of factors unrelated to cancer. Local recurrence and distant metastasis occurred in 6 patients, of whom 3 were still alive for an average of 20.7 months. Three patients died of cancer progression after 9, 19, and 21 months. The survival rate for all 25 patients at 50 months was 77%. Nausea and vomiting occurred in most patients during the administration of cis-platinum. Mild myelosuppression developed in a few patients subjected to protocol 2. Our results indicate that adjuvant chemotherapy consisting of the administration of cis-platinum alone or in combination with other chemotherapeutic agents appears to be effective in patients with invasive bladder cancer.
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PMID:Adjuvant chemotherapy for invasive bladder cancer. 311 97

Cathepsin D is a widely expressed aspartyl lysosomal protease. Clinical studies in several tumor types have shown a strong correlation between cathepsin D expression and tumor progression. In breast carcinoma, its expression is an independent prognostic factor associated with an increased risk of death. However, there have been no studies evaluating cathepsin D in bladder tumors. Therefore, the aim of this study was to determine the pattern of expression of cathepsin D in a large series of bladder carcinomas and assess its role as a prognostic factor against established variables. The tumors from 105 patients (median age 73) (median follow-up 26 months) with transitional cell carcinoma of bladder were examined. Forty-nine patients had superficial tumors (16 pTa; 33 pT1), 56 had invasive tumors (14 pT2; 42 pT3); there were 35 grade 1/2 tumors and 70 grade 3 tumors. These were stained by a standard immunohistochemical technique with an anti-cathepsin D monoclonal antibody. All 4 normal bladder specimens were positive for cathepsin D. Fifty-four tumors (51%) were positive for cathepsin D and 51 (49%) were negative. Chi square analysis showed a significant positive relationship between negative cathepsin D expression and stage (p < 0.0005), grade (p < 0.0001) and tumor morphology (p = 0.001). There was no relationship between cathepsin D expression and tumor ploidy (p > 0.1) or patient age (p = 0.09). Univariate analysis of disease-free and overall survival showed that negative cathepsin D expression (p = 0.01 and p = 0.0003 respectively), stage (p = 0.004 and p < 0.005 respectively) and grade (p = 0.02 and p = 0.0007 respectively) were associated with significantly worse prognosis. However, in a multivariate analysis of age, stage, grade and cathepsin D expression, only stage remained significant for overall survival (p < 0.005). The observed result for cathepsin D in the univariate analysis is probably due to its strong association with grade and stage. Nevertheless, cathepsin D status was able to provide additional prognostic information for overall survival in invasive tumors when stratifying for grade (p = 0.047), which suggests that it might provide additional prognostic data within particular tumor stages.
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PMID:An immunohistochemical and prognostic evaluation of cathepsin D expression in 105 bladder carcinomas. 777 37

In 127 patients with urothelial carcinoma of the bladder the ploidy, deoxyribonucleic acid (DNA) heterogeneity and counts of cell cycle phases in the tumor were analyzed by means of single cell DNA cytophotometry with the intention of finding new prognostic factors in addition to those already known (stage and grade). Patients were followed for 1 to 9 years. The results of the DNA analyses were related to the tumor categories, histopathological grading of the tumor and clinical course. Tumors were histologically classified as grade 1--DNA frequency peaks in the diploid range, grade 2--heterogenous DNA distribution patterns, and grade 3-73% aneuploid and 27% tetraploid DNA values. The proliferation rate of the tumor cells was statistically greater in cases of histological grades 2 and 3 malignancy than in grade 1 malignancy. There was also a positive correlation between tumor stage and DNA ploidy. The cell lines were aneuploid in 38% of the patients with stage pT1, 64% with stage pT2 and almost 85% with stage pT3 tumors. A significant correlation was found between the results of DNA cytophotometry and the clinical course of the disease. Patients with diploid tumor cell lines had no metastases and no local tumor progression for up to 9 years, whereas patients with multiple aneuploid tumor cell lines suffered recurrence and local tumor progression within 6 to 36 months. On the average, the patients died of the tumors 26 months after primary diagnosis. The difference in tumor recurrence and in tumor progression between patients with aneuploid and diploid tumors was highly significant (p < 0.001). The prognosis for patients with grade 1 tumors is good, whereas it is unfavorable in the case of grade 3 tumors. For these 2 groups DNA ploidy affords no additional prognostic information. Grade 2 tumors, on the other hand, are heterogeneous in respect to DNA ploidy, although they exhibit the same degree of histomorphological differentiation. These tumors can be subclassified as aneuploid (biologically aggressive) and diploid or tetraploid (biologically less aggressive). In terms of multivariate Cox regression analysis, DNA ploidy compared with grade and tumor stage was the strongest predictor of survival.
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PMID:Deoxyribonucleic acid content and survival rates of patients with transitional cell carcinoma of the bladder. 825 29

A deletion analysis of chromosome 3 was conducted in 72 cases of transitional cell carcinoma of the urinary bladder using seven microsatellites spanning the 3p arm and two additional microsatellites in 3q. Results showed that 19 of 72 (26.4%) cases had deletions in one or more 3p regions. Two regions of frequent deletion were identified: 3p12-14 and 3p21-23. Less frequent deletions at 3p24.2-25 were also observed. Deletions at 3p were weakly correlated with tumor grade, but strongly with pathological stage. Among 70 cases with histological grade available, 4 of 29 (13.8%) grade 1 and 2 tumors, and 15 of 41 (36.6%) grade 3 tumors showed allelic losses in one or more of the 3p regions studied (P = 0.055). Among 69 cases with pathological stage available, none of 27 superficial carcinomas (pTa, pTis, and pT1) showed 3p deletions, whereas 18 of 42 (42.9%) muscle invasive lesions (pT2, pT3, and pT4) displayed allelic losses at 3p (P < 0.001). In addition, 12 cases showed microsatellite instability, but there was no correlation between abnormalities and tumor grade or stage. No correlation was found between deletions at 3p21-23 and microsatellite instability. In conclusion, deletions at three discrete regions of 3p were identified in bladder carcinoma, suggesting the involvement of candidate tumor suppressor genes residing in these regions. Moreover, detection of allelic losses in these regions was associated with higher tumor grade and more advanced stage, suggesting their potential involvement in bladder tumor progression.
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PMID:Chromosome 3 allelic losses and microsatellite alterations in transitional cell carcinoma of the urinary bladder. 868 47

Adjuvant therapy after radical prostatectomy should ideally be limited to those patients at greatest risk for cancer recurrence, but identification of these patients remains a challenge. The local control rate in a group of 7494 patients undergoing radical prostatectomy for patients with pT2a disease of 76% is not different to pN+ disease of 80%. 95% of the pT3 patients were pN+ .90% of them received adjuvant treatment but only few patients with organ-confined cancer. A prognostic scoring system was created using the regression coefficients from the Cox multivariate model to classify patients with pathologically organ-confined prostate cancer according to risk of progression. Although tumor volume has traditionally been regarded as the most important prognostic factor in patients with localized prostate cancer, a recent multivariate analysis has shown that tumor volume is not an independent predictor. Moreover, accurate measurement of tumor volume is extremely difficult. Preoperative serum PSA levels, clinical stage, pathological grade and stage, and deoxyribonucleic acid (DNA) ploidy were evaluated by multivariate analysis to determine relative value in predicting treatment failure. Patients with the lowest score had a 92% progression free survival rate at 5 years, compared to only 39% of those with the highest scores. Patients believed to be at higher risk for cancer progression despite having organ confined disease might be targeted for adjuvant therapy and closer surveillance, while those at low risk may be followed less often.
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PMID:[Adjuvant treatment after radical prostatectomy in prostatic carcinoma (pT3 or pTxN+): prognostic factors and results]. 945 84

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

The aim of this study was to investigate whether angiogenic factors influence the occurrence of spontaneous apoptosis in advanced gastric cancer. The apoptotic indices (AIs) of 97 tumors from 97 patients with advanced gastric cancer (pT3, pN0, pM0, Stage II) were analyzed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling (TUNEL) method. Intratumoral microvessel densities (IMVDs) of tumors stained with anti-CD34 monoclonal antibody were quantified under x 200 magnification using computer-assisted image analysis. The expressions of angiogenic factors, such as vascular endothelial growth factor (VEGF), thymidine phosphorylase (dThdPase), transforming growth factor-alpha (TGF-alpha), and p53 were analyzed immunohistochemically and compared with IMVDs and AIs. The mean IMVD of the 97 tumors was 365/mm2 (range 147-990/mm2). The mean AI of tumors was 2.1% (range 0-11.3%). A significant inverse correlation between the AIs and the IMVDs was shown (p = -0.278, P = 0.0064). The mean IMVDs of tumors with high expressions of dThdPase, TGF-alpha, or p53 were significantly higher than those of tumors with low expressions of these factors. The mean AI of tumors with high expressions of dThdPase was significantly lower than that of tumors with low expressions of dThdPase (P = 0.023). However, no significant correlations were detected between AIs and the expression levels of VEGF, TGF-alpha, or p53. In gastric cancer, dThdPase may play an important role in tumor progression by increasing microvessels and by suppressing apoptosis of cancer cells.
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PMID:Correlation between spontaneous apoptosis and the expression of angiogenic factors in advanced gastric adenocarcinoma. 1148 84

The natural course of human prostate cancer is highly variable, and we still lack reliable tools to predict the patient's outcome. Recent publications suggest that the deletion of chromosome 8p22 has an important role for tumor progression in prostate cancer. Totally, 97 patients (41 Japanese and 56 Swedish) were studied to detect the status of chromosome 8p22 deletion by the fluorescence in situ hybridization (FISH) technique. Seventy-seven underwent surgery (59 radical prostatectomies or 18 lymph node dissections), and the specimens were prepared by touch biopsy. Fine-needle aspiration biopsies (FNAB) were obtained from another non-operative 20 cases. Disease progression was evaluated in 57 patients with a median follow-up of 59 months. 8p22 deletions were detected in 58 (60 %) of all cases. The frequency of 8p22 deletion did not significantly differ between different preparations of specimens (touch biopsy vs. FNAB) as well as between different races (Japanese vs. Swedish). Cases with more than pT3 tumors had a significantly higher frequency of 8p22 deletion than those with pT2 (p < 0.01). Multivariate analysis demonstrated that 8p22 deletion was the strongest parameter to predict disease progression (hazard ratio = 5.75; p = 0.0001). Studies on chromosomal deletions of 8p22 by the FISH technique may serve as a universal genetic marker to optimize the treatment strategy in patients with prostate cancer.
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PMID:The role of chromosome 8p22 deletion for predicting disease progression and pathological staging in prostate cancer. 1456 75

To evaluate prognostic value of morphometric studies of the stroma of transitional cell carcinomas of the renal pelvis and ureter, we studied retrospectively the data of primary examination and follow-up of 75 patients (49 males, 65% and 26 females, 35%; mean age 61.9 +/- 1.2 years) given radical surgical treatment for cancer of the renal pelvis and ureter. Five-year survival in the absence of tumor progression was 23%. Morphological examination diagnosed transitional cell carcinoma with invasion pT1, pT2, pT3 and pT4 in 3(4%), 15(20%), 47(63%) and 10(13%) cases and differentiation degree G1, G2, G3 in 31(41%), 15(20%) and 29(39%) cases, respectively. In addition to the standard morphological examination of the tumor, we made morphometry of stromal and tumor area, analysed composition and count of stromal effector cells (lymphocytes, eosinophilic and neutrophilic leukocytes, macrophages, mast and plasmic cells), the degree of stromal vascularization. Prognostic value of the above parameters was estimated according to significance of their correlation with postoperative survival of the patients. The survival correlated with the depth of cancer invasion (p = 0.005) and differentiation of tumor tissue (p = 0.006), high cell infiltration of tumor stroma is prognostically unfavourable (R2 = 0.03; F = 3.41; p = 0.069) as well as weak presentation of stromal component of the tumor (p = 0.056). The lowest survival was observed in patients with cancer of the renal pelvis and ureter with a great number of mast cells (p = 0.056), macrophages (p = 0.037) and neutrophils (p = 0.029) in the tumor stroma. According to the results of multiple regression analysis (R2 = 0.08; F = 5.42; p = 0.024), five-year postoperative survival most closely correlated with cancer invasion depth (p < 0.001), degree of tumor cells differentiation (p < 0.001) and number of macrophages infiltrating tumor stroma (p < 0.001). Significance of survival prognosis for patients with cancer of renal pelvis and ureter can be raised by estimation of mean number of free stromal cells and expression of stromal component.
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PMID:[Prognostic implication of morphometric stromal parameters of renal pelvis and ureteral transitional cell carcinomas]. 1519 6


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