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Under the Superfund Innovative Technology Evaluation (SITE) Program, a technology developed by AWD Technologies, Inc. was demonstrated in September 1990. This paper presents the major results of the SITE demonstration of AWD Technologies' AquaDetox/SVE treatment system designed for simultaneous on-site treatment of contaminated groundwater and soil-gas. The groundwater and soil at the demonstration site were contaminated with trichloroethylene (TCE) and tetrachloroethylene (PCE). The AWD technology was evaluated on the basis of the removal efficiencies of TCE and PCE from the contaminated groundwater and soil-gas. The conclusions drawn from these evaluations are: (1) the system achieved removal efficiencies as high as 99.99 percent for groundwater and 99.9 percent for soil-gas; (2) the effluent groundwater was in compliance with the regulatory discharge requirements of 5 micrograms/L each for TCE and PCE for all test runs; (3) the demonstrated 1,000 gpm system has an estimated capital cost of $4.3 million and annual operating and maintenance cost of approximately $820,000.
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PMID:U.S. EPA SITE demonstration of AWD Technologies' AquaDetox/SVE system. 178 57

We report here the use of multiplex fluorescent polymerase chain reaction (PCR) for quantitative allele loss detection using microsatellites with 2-5 base pair repeat motifs. Allele loss of APC, DCC, p53 and RB1 in colorectal tumours has been reported previously using a variety of methods. However, not all workers used intragenic markers. We have used microsatellite polymorphisms which map within, or are closely linked to, these tumour-suppressor gene loci in order to determine whether these loci are indeed the targets for alteration in colorectal cancer. In addition, we have assayed two other tumour-suppressor genes, WT1 and NF1, to see whether they play a role in colorectal carcinogenesis. The putative metastasis-suppressor gene, NM23, was also investigated since there have been conflicting reports about its involvement in colorectal carcinogenesis. Allele loss was detected at the DCC (29%), p53 (66%), RB1 (50%) and NF1 (14%) loci and in the APC/MCC region (50%), but not at the WT1 or NM23 loci. These rapid, and mostly gene-specific, fluorescent multiplex PCR assays for allele loss detection could be modified to devise a single molecular diagnostic test for the important lesions in colorectal cancer.
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PMID:Frequency of allele loss of DCC, p53, RBI, WT1, NF1, NM23 and APC/MCC in colorectal cancer assayed by fluorescent multiplex polymerase chain reaction. 794 85

We used Southern blot analysis and polymerase chain reaction-based techniques to examine deletions of tumour suppressor gene loci in 91 primary colorectal tumours. The tumour suppressor genes studied were MCC and APC on chromosome 5q, p53 on chromosome 17p, DCC on chromosome 18q, and the putative suppressor gene nm23-H1 on chromosome 17q. The most frequent allelic loss observed was in chromosome 17p with 76% (68/89) of informative tumours showing loss of heterozygosity at this locus, followed by 34% (19/55) for DCC, 31% (12/39) for MCC, 17% (9/53) for APC and 16% (3/19) for nm23. No significant differences in the frequency of these suppressor gene allelic losses were observed between Dukes B and C stage adenocarcinomas.
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PMID:Loss of heterozygosity of tumour suppressor gene loci in human colorectal carcinoma. 808 Jun 84

Fluorescent polymerase chain reaction (PCR) was used to assay 12 microsatellite markers (APC x 2, DCC, P53 x 2, RB1, NM23, WT1, D6S260, D6S262, D6S281 and TNFa) to look for evidence of microsatellite instability in 40 cases of follicle centre cell lymphoma (FCC). Evidence of novel alleles seen in the tumour tissue but not the normal uninvolved tissue was seen in seven cases (17%). In only two of these cases (5%) was more than one locus involved but in these cases multiple affected loci were seen (4/12 and 7/12 respectively). The detection of microsatellite instability indicates a DNA repair defect such as that which would be predicted to occur in cells with mutated mismatch repair genes, a novel finding in FCC lymphoma.
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PMID:Microsatellite instability in follicle centre cell lymphoma. 861 53

The investigation of molecular evidence of gastric carcinoma will be contributable to the prevention, gene diagnosis and therapy of human gastric neoplasms. To determine the specific genetic change in human gastric cancer (HGC) and precancerous lesions, we analysized FISH, PCR/SSCP, IHC and DNA sequencing by using multiple probes to detect the gene abnormalities (mutation, deletion, amplification or overexpression of genes) of 67 fresh tumors, 63 endoscopic biopsies including 30 dysplasia (DYS) and 33 intestinal metaplasia (IM, and 4 tumor cell lines from HGC patients. Multiple genetic abnormalities including hypomethylation of H-ras gene, amplification and overexpression of met and erbB2, deletion of APC, mts1/p16, p53 and nm23 gene and point mutation of p53 gene were noted in HGC and precancerous lesion of human gastric mucosa. Among these changes, p53 gene was the highest frequence genetic alteration in 39/67 (54-58%) of gastric carcinoma. These results indicate that overexpression of met and H-ras occurs at early stage in progression of neoplasia, amplification of met, erbB2 and akt2 gene occurs at progressing stage of tumorigenesis, deletion of p53, APC, mts1/p16 and nm23 occurs at advanced stage in the progression of cancer. The abnormalities should be associated with malignant phenotypes: poor differentiation, vascular invasion, lymph nodes metastasis, and low survival time. We detected p53 gene mutation in both cancer and precancerous lesions of IM and DYS. These results suggest that p53 may be a susceptible gene and alteration of p53 gene plays an important role in the development of HGC.
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PMID:[Multiple gene alterations involved in the processor of human gastric carcinogenesis]. 869 90

We have examined 41 cases of follicle centre cell lymphoma with fluorescent PCR of microsatellite repeats closely linked to or within six tumour suppressor gene loci (APC, DCC, P53, RB1, WT1 and NM23). These probes are highly informative with heterozygousity rates in the range of 57%-90%. In addition we have used four loci from chromosome 6 (D6S260, TNFa, D6S281 and D6S262) as control loci which are unlikely to be involved in the pathogenesis of lymphoma. Of 369 informative PCR reactions allele imbalance was identified in 38 (10%) and this was seen in 23 of the 41 cases. Looking at individual loci allele imbalance was seen in APC(1) 11%, APC(2) 12%, P53(1) 5%, P53 (2) 7%, WT1 5%, RB1 13%, DCC 18% and NM23 0%. This frequency of change was no different from that seen at the control loci D6S260 16%, TNFa 20%, D6S281 4% and D6S262 9%. In the indolent phase of germinal centre cell lymphoma there is therefore quite a high rate of allele imbalance at all loci but this is no higher in those loci linked to tumour suppressor genes.
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PMID:Allele imbalance at tumour suppressor loci during the indolent phase of follicle centre cell lymphoma. 872 37

Defining boundaries of chromosomal rearrangements at the molecular level would benefit from landmarks that link the cytogenetic map to physical, genetic, and transcript maps, as well as from large-insert FISH probes for such loci to detect numerical and structural rearrangements in metaphase or interphase cells. Here, we determined the locations of 24 genetically mapped CEPH-Mega YACs along the FLpter scale (fractional length from p-telomere) by quantitative fluorescence in situ hybridization analysis. This generated a set of cytogenetically mapped probes for chromosome 17 with an average spacing of about 5 cM. We then developed large-insert YAC, BAC, PAC, or P1 clones to the following 24 known genes, and determined refined map locations along the same FLpter scale: pter-TP53-TOP3-cen-TNFAIP1-ERBB2-TOP2A- BRCA1-TCF11-NME1-HLF-ZNF147/CL N80-BCL5/MPO/SFRS1-TBX2-PECAM1-DDX5/ PRKCA-ICAM2-GH1/PRKAR1A-GRB2-CDK3 /FKHL13-qter. Taken together, these 48 cytogenetically mapped large-insert probes provide tools for the molecular analysis of chromosome 17 rearrangements, such as mapping amplification, deletion, and translocation breakpoints in this chromosome, in cancer and other diseases.
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PMID:Molecular cytogenetic mapping of 24 CEPH YACs and 24 gene-specific large insert probes to chromosome 17. 985 13

Analysis of loss of heterozygosity (LOH) is very important in the study of tumor suppressor genes. However, accurate LOH analysis of tumor suppressor genes is difficult because of dilution by contaminating non-tumor DNA. Thus, enrichment of tumor DNA is required to accurately determine LOH of the tumor. We developed a new application of the fluorescent polymerase chain reaction by coupling it with crypt isolation to accurately assess the incidence of LOH of tumor suppressor genes in 45 colorectal carcinomas. LOH was observed at p53 in 26 of 37 tumors (70.3%), at APC in 13 of 35 (37.1%), at DCC in 16 of 25 (64.0%), at NF-2 in 5 of 23 (21.7%), and at nm23 H-1 in 7 of 30 (23.3%). We could clearly determine LOH of these genes because the crypt isolation technique was used. Although the incidence of LOH at each of these loci, as determined by using this technique, was similar to that obtained in previous studies using conventional methods, this method provides a simpler, more accurate way to assess LOH. In addition, the morphology of the samples can be analyzed before genetic analysis.
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PMID:Use of crypt isolation to determine loss of heterozygosity of multiple tumor suppressor genes in colorectal carcinoma. 1072 18

Although the genetic basis for gallbladder carcinogenesis has not been clarified, considerable evidence has shown that genetic alterations play an important role in the development and progression of human cancers. In this study, we analyzed 30 gallbladder carcinomas to investigate the role of genetic alterations in their tumorigenesis, and to study correlations with their clinicopathological features. Tissue samples were obtained from 30 patients with gallbladder carcinoma (11 men and 19 women; mean age, 62 years; age range, 38-80 years). Genomic DNAs were extracted from fresh tumor tissue. We examined loss of heterozygosity (LOH) in the p53, APC, DCC, RB, and NM23-H1 gene regions by polymerase chain reaction (PCR)-LOH assay using an automated fluorescent DNA sequencer employing four microsatellite markers (p53, APC, DCC, NM23-H1). Five additional microsatellite markers were used for the determination of microsatellite instability (MSI). LOH was found at p53 in 9 of 15 informative cases (60%), at DCC in 10 of 22 (45%), at APC in 5 of 15 (33%), at RB in 1 of 8 (13%), and at NM23-H1 in 1 of 15 (7%). MSI was observed in 5 of 30 cases (17%) in at least one chromosomal loci of these nine microsatellite markers. None of the patients with MSI-positive tumors showed lymph node metastasis, and there was an inverse correlation between MSI and the presence of LOH in gallbladder carcinoma. These results suggest that there are two independent genetic pathways in gallbladder carcinogenesis; that is, an MSI pathway and an LOH pathway.
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PMID:Microsatellite instability in gallbladder carcinoma: two independent genetic pathways of gallbladder carcinogenesis. 1106 28

Multiple genetic and epigenetic alterations in oncogenes, tumour-suppressor genes, cell-cycle regulators, cell adhesion molecules, DNA repair genes and genetic instability as well as telomerase activation are implicated in the multistep process of human stomach carcinogenesis. However, particular combinations of these alterations differ in the two histological types of gastric cancer, indicating that well-differentiated or intestinal-type and poorly differentiated or diffuse-type carcinomas have distinct carcinogenetic pathways. In the multistep process of well-differentiated-type carcinogenesis, the genetic pathway can be divided into three subpathways: an intestinal metaplasia-->adenoma-->carcinoma sequence, an intestinal metaplasia-->carcinoma sequence and de novo. In the multistep process of well-differentiated-type or intestinal-type gastric carcinogenesis, infection with Helicobacter pylori may be a strong trigger for hyperplasia of hTERT-positive 'stem cells' in intestinal metaplasia. Genetic instability and hyperplasia of hTERT-positive stem cells precede replication error at the D1S191 locus, DNA hypermethylation at the D17S5 locus, pS2 loss, RARbeta loss, CD44 abnormal transcripts and p53 mutation, all of which accumulate in at least 30% of incomplete intestinal metaplasias. All of these epigenetic and genetic alterations are common events in intestinal-type gastric cancer. An adenoma-->carcinoma sequence is found in about 20% of gastric adenomas with APC mutations. In addition to these events, p53 mutation and loss of heterozygosity (LOH), reduced p27 expression, cyclin E expression and the presence of c-met 6.0-kb transcripts allow malignant transformation from the above precancerous lesions to intestinal-type gastric cancer. DCC loss, APC mutations, 1q LOH, p27 loss, reduced tumour growth factor (TGF)-beta type I receptor expression, reduced nm23 expression and c-erbB gene amplification are frequently associated with an advanced stage of intestinal-type gastric cancer. The de-novo pathway for carcinogenesis of well-differentiated gastric cancer involves LOH and abnormal expression of the p73 gene that is responsible for the development of foveolar-type gastric cancers with pS2 expression. On the other hand, LOH at chromosome 17p, mutation or LOH of p53 and mutation or loss of E-cadherin are preferentially involved in the development of poorly differentiated gastric cancers. In addition to these changes, gene amplification of K-sam, and c-met and p27 loss as well as reduced nm23 obviously confer progression, metastasis and diffusely productive fibrosis. Mixed gastric carcinomas composed of well-differentiated and poorly differentiated components exhibit some but not all of the molecular events described so far for each of the two types of gastric cancer. Besides these genetic and epigenetic events, well-differentiated and poorly differentiated gastric cancers also organize different patterns of interplay between cancer cells and stromal cells through the growth factor/cytokine receptor system, which plays an important role in cell growth, apoptosis, morphogenesis, angiogenesis, progression and metastasis. Meta-analysis of epidemiological studies and animal models show that both intestinal and diffuse types of gastric cancer are equally associated with H. pylori infection. However, H. pylori infection may play a role only in the initial steps of gastric carcinogenesis. Differences in H. pylori strain, patient age, exogenous or endogenous carcinogens and genetic factors such as DNA polymorphism and genetic instability may be implicated in two distinct major genetic pathways for gastric carcinogenesis.
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PMID:Genetic pathways of two types of gastric cancer. 1505 5


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