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Query: UMLS:C0005684 (bladder cancer)
 16,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this review article some novel immunotherapeutic models as well as some new concepts concerning the unspecific and specific T-cell stimulation are discussed briefly. Some of these immunotherapeutic models are restricted to bladder cancer; the others have a generalized meaning. One model, restricted to bladder cancer, is based on the enzymatic++ pretreatment of effector-cells (macrophages, NK-cells), followed by their instillation in the patient's bladder. The other bladder tumor restricted model includes the direct in situ activation of effector cells by proteases and lipases. A third model for the treatment of bladder tumor implies a presensitization of patient's TD/TDTH-cells, followed by the treatment of patient's bladder tumor cells by some, common haptenic group. In addition, some novel ways of immune stimulation, partly by circumventing the (tumor-specific) immune tolerance, based on the cross-linking of crucial membrane structures on T4- and T8-cells or on a managed, controlled APC: T-cell interaction, are discussed. The details inclusively the comprehensive special literature can not be brought in this review article; they should be dealt with in special papers being in preparation.
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PMID:[Novel immunotherapeutic models for neoplastic diseases of the urogenital tract with special attention to bladder carcinoma]. 257 84

We examined 24 human bladder cancer tissues for possible mutations in the entire coding region of the human DNA polymerase beta gene using polymerase chain reaction analysis, single-strand conformational polymorphism analysis of RNA, and sequence analysis. DNA polymerase beta gene mutations were observed in four of the 24 cases (16.7%) and included three missense point mutations and a single base insertion. The single base insertion was also observed in our previous study of human prostate cancer, suggesting that this region may be a hot spot for mutation of the DNA polymerase beta gene. No clinical or pathological association was found among the four cases that contained the mutation. Three of the four cases with DNA polymerase beta gene mutation had mutations of the p16 or RB genes or loss of heterozygosity of the p53 and APC gene loci. The results of the study presented here suggest that DNA polymerase beta gene mutations, in combination with mutations of tumor suppressor genes, may be involved in certain cases of human bladder cancer.
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PMID:DNA polymerase beta gene mutations in human bladder cancer. 856 64

Current histopathological evidence suggests that gall-bladder cancer has two main morphological pathways for its development: de novo (ab initio) origin and adenoma-carcinoma sequence. In order to investigate the genetic difference between them, APC mutations were examined by RNase protection analysis, K-ras mutations by nested polymerase chain reaction-restriction fragment length polymorphism analysis, and p53 gene overexpression by immunohisto-chemical analysis in both tumors and benign lesions of the gall-bladder. Overexpression of the p53 gene was detected in 105 of 164 (64%) de novo carcinomas regardless of size and depth of invasion, but not in 16 tumors of carcinoma-in-pyloric-gland-type adenoma, or in 51 adenomas (47 pyloric gland-type and 4 intestinal-type). K-ras codon 12 mutation was detected in 4 of 40 (10%) de novo carcinomas, all four being associated with p53 gene overexpression, but not in 12 tumors of carcinoma in adenoma or 16 adenomas (14 pyloric gland-type and 2 intestinal-type). APC mutation was not found in 16 de novo carcinomas or the one pyloric gland-type adenoma examined. These results suggest that there are two distinct genetic pathways in gall-bladder carcinogenesis; that is, de novo carcinoma develops from a predominant p53 alteration with low K-ras mutation, and carcinoma-in-pyloric-gland-type adenoma develops from p53-, K-ras-, and APC-gene-unrelated, as yet unknown, alteration.
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PMID:APC, K-ras codon 12 mutations and p53 gene expression in carcinoma and adenoma of the gall-bladder suggest two genetic pathways in gall-bladder carcinogenesis. 880 79

Familial adenomatous polyposis coli (FAP) has been shown to be associated with germline mutations of the adenomatous polyposis gene (APC) on chromosome 5. Extra-colonic manifestations also occur in FAP and include desmoid tumors, epidermoid cysts and osteomas. The combination of FAP with extracolonic symptoms is commonly referred to as Gardner's syndrome. It remains difficult, however, to predict which patients may have a propensity to develop extracolonic manifestations. The rapid acetylation phenotype is believed to be associated with an increased likelihood of sporadic colorectal cancer, whereas the slow acetylation phenotype is recognized as a predisposing factor for bladder cancer. The slow acetylation phenotype is caused by mutant alleles of the cytosolic enzyme N-acetyltransferase (NAT2). In this study, we determined the NAT2 genotype in members of one large FAP family and three smaller ones all of which had been shown to harbor the same germline APC gene mutation. We observed a significant correlation between slow acetylation genotypes and extracolonic manifestations of the disease. Rapid acetylation genotypes were not overrepresented in colorectal cancer cases in this family as compared to the frequency of this genotype in the normal Caucasian population.
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PMID:Association of extracolonic manifestations of familial adenomatous polyposis with acetylation phenotype in a large FAP kindred. 915 20

We investigated the aberrant promoter methylation profile of bladder cancers and correlated the data with clinicopathological findings. The methylation status of 10 genes was determined in 98 surgically resected bladder cancers, and we calculated the median methylation index (MI), a reflection of the methylated fraction of the genes tested. Methylation frequencies of the genes tested in bladder cancers were 36% for CDH1, 35% for RASSF1A and APC, 29% for CDH13, 16% for FHIT, 15% for RAR beta, 11% for GSTP1, 7% for p16(INK4A), 4% for DAPK, and 2% for MGMT. Methylation of four of the individual genes (CDH1, RASSF1A, APC, and CDH13) and the MI were significantly correlated with several parameters of poor prognosis (tumor grade, growth pattern, muscle invasion, tumor stage, and ploidy pattern). Methylation of CDH1, FHIT, and a high MI were associated with shortened survival. CDH1 methylation positive status was independently associated with poor survival in multivariate analyses. Our results suggest that the methylation profile may be a potential new biomarker of risk prediction in bladder cancer.
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PMID:Aberrant promoter methylation profile of bladder cancer and its relationship to clinicopathological features. 1175 81

Urothelial carcinomas (TCC) constitute the vast majority of bladder cancers in most of the world. On the other hand, squamous cell bladder carcinoma, a rare subtype in the Western world, is a common subtype in areas with endemic Schistosoma infection. Although schistosomal infection has been reported to influence DNA methylation, the pattern and extent of CpG island hypermethylation in squamous cell carcinomas remain unknown. In this study, we used methylation-specific PCR to characterize 12 cancer-related genes in 41 bladder cancer samples from Egypt (31 squamous cell carcinomas (SCC), 21 of them associated with Schistosoma and 10 TCC, five of which were Schistosoma-associated). The genes analyzed included E-cadherin, DAP-Kinase, O6MGMT, p14, p15, p16, FHIT, APC, RASSF1A, GSTP1, RARbeta and p73. Methylation of at least one gene was detected in all squamous cell tumors except two, and 45% of samples had at least three methylated genes. The average methylation index was 0.24, corresponding to three of the 12 analyzed genes. Schistosoma-associated tumors had more genes methylated than non-Schistosoma tumors (average MI: 0.29 vs 0.14) (P = 0.027). Although the extent of methylation in TCC (average MI: 0.16) was lower than in squamous cell carcinomas (SCC), the overall profile of methylation was similar, with Schistosoma-associated cases having a higher methylation index. Our results suggest that schistosomal involvement associates with a greater degree of epigenetic changes in the bladder epithelium.
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PMID:CpG island methylation in Schistosoma- and non-Schistosoma-associated bladder cancer. 1515 12

The role of promoter methylation in the process of cancer cell metastasis has, however, not yet been studied. Recently, methylation of the TPEF (transmembrane protein containing epidermal growth factor and follistatin domain) gene was reported in human colon, gastric, and bladder cancer cells. Using the Methylight assay, TPEF/HPP1 gene methylation was assessed in primary colorectal cancers (n = 47), matched normal colon mucosa, as well as in the liver metastasis of 24 patients with colorectal cancer, and compared to the methylation status of the TIMP-3, APC, DAPK, caveolin-2, and p16 genes. TPEF was frequently methylated in primary colorectal cancers (36 of 47) compared to the normal colon mucosa (1 of 21) (P < .0001), and TPEF mRNA expression in colon cancer cell lines was restored after treatment with 5-aza-2'-deoxycytidine. The p16 and APC genes were also frequently methylated in primary colorectal cancers (P < .02) compared to the normal colon mucosa. Interestingly, promoter methylation was significantly more frequent in proximal, nonrectal cancers (P < .05). Furthermore, a high degree of methylation of the TPEF gene was also observed in liver metastasis (19 of 24). In summary, we observed frequent TPEF methylation in primary colorectal cancers and liver metastases, indicating that epigenetic alterations are not only present in the early phases of carcinogenesis, but are also common in metastatic lesions. The high frequency of TPEF methylation in this series of colorectal cancers underscores the importance of epigenetic changes as targets for the development of molecular tests for cancer diagnosis.
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PMID:Hypermethylation of the TPEF/HPP1 gene in primary and metastatic colorectal cancers. 1620 79

Tumour suppressor gene (TSG) methylation has been proposed as a diagnostic marker for urothelial cancer (UC). Here, we compare the frequency of urinary TSG methylation in young and elderly patients, with and without UC. Urine samples were obtained prospectively from 35 UC patients, 35 benign controls over the age of 70 years and 34 healthy volunteers under the age of 40 years. Methylation analysis was performed for eight gene promoters using quantitative methylation-specific PCR. Methylation was detected in urine DNA from all three patient groups. The highest frequencies were seen in UC patients. Significantly less methylation was present in control samples than UC cases for RASSF1a and APC (P < 0.034). The 'methylation index' and level of methylation was highest in the UC group and lowest in the young control group. A marker panel of RASSF1a, E-cad and APC generated a sensitivity of 69%, a specificity of 60% and a diagnostic accuracy of 86%. TSG methylation is detectable in urine DNA from patients with and without bladder cancer. The frequency and extent of methylation appears to increase with age and malignancy. The lack of tumour specificity suggests that further investigation is required before this test is introduced into clinical practice.
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PMID:Methylational urinalysis: a prospective study of bladder cancer patients and age stratified benign controls. 1628 22

The multistep development of malignant tumors with increasing accumulation of genetic alterations from preneoplastic lesions to invasive carcinoma is an accepted model of carcinogenesis. Urothelial carcinoma of the bladder and upper urinary tract is an interesting model system to study tumor development and progression. There is both clinical and molecular evidence that urothelial carcinoma can be divided in two groups with different characteristics: 1) well differentiated genetic stable and mostly superficial papillary tumors with frequent recurrence and low progression risk and 2) poorly differentiated mostly solid and invasive tumors with a high number of genetic alterations. The aim of the studies summarized in this manuscript were: 1) to identify genetic changes with importance for urothelial carcinogenesis by investigation of preneoplastic and early neoplastic urothelial lesions, 2) to define molecular markers for progression of papillary carcinoma, and 3) to investigate the importance of microsatellite instability and mismatch repair defects for development of tumors of the upper urinary tract which are frequently found within the HNPCC syndrome. The investigation of urothelial hyperplasias, dysplasias and carcinoma in situ by deletion mapping (LOH analysis), FISH, CGH and mutation detection revealed that urothelial hyperplasias are precursors of papillary bladder tumors and flat dysplasias can be regarded as precursors of solid bladder cancers. In bladder cancer patients, there are genetic alterations already detectable in histologically inconspicous urothelium. The investigation of papillary bladder cancers for progression-related genetic alterations showed that mutations in the wnt pathway genes APC and beta-Catenin do not play an important role in urothelial carcinogenesis. Instead, the expression of the antagonistic wnt-related genes WIF-1 and sFRPI is strongly reduced in bladder cancer and associated with poor prognosis in papillary tumors. Loss of sFRP1 expression is not due to gene mutation but to epigenetic inactivation by promoter hypermethylation and is related to deletions at chromosome 8p12. In contrast to bladder cancers, tumors of the ureter and renal pelvis develop through a different genetic pathway in 30% of cases. The loss of mismatch repair proteins (hMSH2, hMLH1 or hMSH6) leads to a mutator phenotype with accumulation of genetic alterations in multiple repetitive sequences (microsatellite instability, MSI). MSI-positive tumors were predominantly located in the ureter and showed a lower tumor stage and grade and papillary and frequently inverted growth pattern. They were more frequent in females and younger patients and had a higher incidence of colorectal carcinomas and other tumors in the family. Chromosome 9 deletions, a hallmark of urothelial carcinomas, and the number of chromosomal alterations as detected by CGH analysis were significantly less frequent in these tumors. These data strongly suggest a distinct molecular pathway in the development of upper urinary tract tumors with mutator phenotype.
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PMID:[Molecular changes in development and progression of urothelial carcinoma]. 1688 10

Here, we report on a patient with squamous cell carcinoma (SCC) arising from recurrent anal fistula. The patient was a 57-year-old woman who had 32-year history of having a recurrent perianal abscesses that ruptured spontaneously. Six months before her admission to our hospital, anal pain developed. She had no history of inflammatory bowel disease. Physical examination revealed three external fistulous openings at the two o'clock position, 2 cm from the anal verge. One internal opening in the lower rectum was found with proctoscopy. The patient underwent fistulectomy. Microscopic examination showed SCC arising from the anal fistula, which was accompanied by vessel invasion. The tumor was observed to be continuous from the external opening but was not exposed to the internal opening of the rectal mucosa. Because human papillomavirus (HPV) infection was suspected, immunohistochemical analysis was performed, but showed no HPV infection. Two weeks after fistulectomy, abdominoperineal resection with lymph node dissection was performed. Histopathological examination revealed no remnant cancer tissue or lymph node metastasis. She was discharged after surgery without complications. Eight years after the operation, she complained of constant pain during micturition. Urological examination revealed urinary bladder cancer, and transurethral resection of the bladder tumor was performed. Histopathological examination revealed transitional cell carcinoma of the urinary bladder. Two years later, the patient died of metastatic urinary bladder cancer, without recurrence of the fistula cancer. Because the patients mother had died of urinary bladder cancer and she herself had metachronous urinary bladder cancer in addition to fistula cancer, we investigated whether microsatellite instability (MSI) and chromosomal instability correlated with fistula cancer development. Immunohistochemical analysis of formalin-fixed, paraffin-embedded surgical tumor specimens for p53, MLH1, and MSH2 was performed. The tumor specimens showed no MLH1 expression but did show normal MSH2 expression. p53 was not expressed. Five microsatellite loci were examined using the tumor specimens to detect MSI, namely two loci with mononucleotide runs (i.e., BAT25 and BAT26) and three loci with dinucleotide repeats (i.e., APC, Mfd15, and D2S123). The tumor specimens showed alternations in the repeated sequences of two loci (i.e., BAT26 and D2S123). As a result, the tumor was classified as MSI-H (high) according to the Bethesda criteria. Our patient had MSI and one of the smallest reported SCCs arising from recurrent anal fistulae.
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PMID:Squamous cell carcinoma arising from recurrent anal fistula. 1787 4


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