Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alterations of cell-surface glycoconjugates have been associated with invasiveness and metastatic capacity in a number of experimental and human tumors (bladder and colon cancer). We have recently shown that human melanoma cells from variants selected for high metastatic potential in an animal model bind the lectin peanut agglutinin (PNA), and that human melanoma cell populations enriched for PNA binding cells generated a higher frequency of metastases when xenografted into immune suppressed neonatal rats. We have therefore sought cells binding PNA in biopsied human melanocytic tumors and compared frequencies of PNA binding by cells from benign nevi, early and late primary melanomas, and metastatic melanomas. Sections of conventionally processed tissues were deparaffinised and exposed to biotinylated PNA; PNA fixation was revealed by the avidine/peroxidase/AEC technique. In 51 specimens tested, PNA appears to react electively with invasive tumors, since only one of the 7 early primary melanomas (Clark I-II) reacted while 13/23 late primary melanomas (Clark III-V), and 4/21 melanoma metastases were reactive. In addition, only 1/17 benign nevi bound PNA. In primary tumors, the reactive cells were exclusively invasive tumors cells in the dermis. PNA reactive material was observed in the cytoplasm and plasma membrane of reactive cells. Hence, alterations in composition and cellular localisation of glycoconjugates detectable by lectin histochemistry in melanoma cells may be markers of metastatic potential that may be applicable on an individual patient basis.
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PMID:Selective expression of PNA-binding glycoconjugates by invasive human melanomas: a new marker of metastatic potential. 776 55

We have developed a new immunochemical test for fecal lactoferrin (LF) utilizing an enzyme-linked immunosorbent assay (ELISA). The ELISA had a sensitivity of about 10 micrograms/L of lactoferrin and the measurable range was 10.0-1000.0 micrograms/L (1.0-100.0 micrograms LF/g feces). The stability of lactoferrin in feces was greater than that of myeloperoxidase and leucocyte elastase. The fecal concentration of lactoferrin (mean +/- SD) in 35 normal subjects was 0.75 +/- 0.83 microgram/g feces, whereas that in 24 patients with colon cancer was 74.4 +/- 88.3 micrograms/g feces. The fecal lactoferrin concentration of 38 patient with active ulcerative colitis was 307.4 +/- 233.9 micrograms/g feces, and that in 36 patients with active Crohn's disease was 191.7 +/- 231.1 micrograms/g feces. The ELISA for human fecal lactoferrin might be useful in the diagnosis of colon disease.
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PMID:Immunochemical detection of human lactoferrin in feces as a new marker for inflammatory gastrointestinal disorders and colon cancer. 800 Dec 86

KL-6, a circulating mucin-like glycoprotein, is a pulmonary adenocarcinoma-associated antigen and is also regarded as an indicator of disease activity of interstitial pneumonitis. KL-6 has extensive heterogeneous antigenic determinants and consists of multiple heterogeneous antigen molecules. We have searched for circulating KL-6-associated glycoproteins with superior diagnostic value to KL-6 as a tumor marker for pulmonary adenocarcinoma. A new murine monoclonal antibody EH-123 reacting with an asialosugar chain on KL-6 was established. A new KL-6-associated molecule detected by a bimonoclonal bideterminant sandwich assay using the EH-123 antibody as a catcher and horseradish peroxidase-labeled KL-6 as a tracer was designated as CAM 123-6. In 59% (22 of 37) of patients with pulmonary adenocarcinoma, serum levels of CAM 123-6 were abnormally elevated and the positive rate increased with the progression of clinical stage. Elevated levels were not detected in normal individuals or in patients with benign lung diseases, other histologic types of lung cancer, gastric cancer, colon cancer or breast cancer. CAM 123-6 was more specific to pulmonary adenocarcinoma than carcinoembryonic antigen (CEA), but the sensitivity of CAM 123-6 for pulmonary adenocarcinoma was similar to that of CEA. CAM 123-6 is a promising candidate as a serum tumor marker for pulmonary adenocarcinoma.
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PMID:A new serum tumor marker, CAM 123-6, highly specific to pulmonary adenocarcinoma. 814 2

To examine the influence of hypercholesteremia on 1,2-dimethylhydrazine (DMH)-induced rat colon cancer, Sprague-Dawley rats received dietary cholesterol (CH, 0-2%) and cholic acid (CA, 0.25%) with or without DMH (20 mg/kg, s.c. injection) for 18 weeks. The rats receiving dietary cholesterol and cholic acid all significantly increased total serum cholesterol and lipids but only a high cholesterol diet (2% CH plus 0.25% CA) decreased the activity of glutathione peroxidase (GSH-Px) and increased the formation of peroxides in the colon (P < 0.01). The rats that received the combination of DMH and high cholesterol diet enhanced these effects. At the end of the experiment, the diet group administered DMH and high cholesterol (2% CH plus 0.25% CA) developed colon adenoma at 50% of incidence in pathological examination, but no colon adenoma formed in the rats treated with high cholesterol alone. It is supposed that a non-carcinogenic agent like cholesterol may potentiate the carcinogenicity of DMH in rats via an increase of lipid peroxidation and decrease in the activity of peroxidase in the target organ.
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PMID:Promotion of colon carcinogenesis through increasing lipid peroxidation induced in rats by a high cholesterol diet. 862 Apr 57

In contrast to normal colorectal mucosa, peanut-agglutinin-(PNA)-reactive glycoconjugates are commonly expressed in most colorectal carcinomas and in some pre-malignant conditions such as adenomas and ulcerative colitis. Since enzymatically detectable galactose-beta1-3-N-acetyl-galactosamine residues are found in rectal mucus obtained from patients with carcinoma of the large bowel, it was investigated here whether PNA-reactive carbohydrate structures in rectal mucus can be exploited in the detection of colorectal neoplasia. Samples of rectal mucus obtained from 261 randomly selected patients with colorectal symptoms were applied on nitrocellulose filters. The presence of PNA-reactive glycoconjugates in mucus samples was determined by a peroxidase-conjugated PNA-overlay procedure. The results were correlated to findings from total colonoscopy/surgery and histopathology. PNA-reactive carbohydrate structures were detected in 76% of patients with carcinoma (p < 0.005), in 62% of patients with adenoma (p < 0.005), in 69% of patients with inflammatory bowel disease (p < 0.005), and in 38% of patients with hyperplastic polyps (NS), in contrast to 21% of the control subjects with macroscopically normal colorectal mucosa. These results show that PNA-reactive carbohydrate alterations in rectal mucus correlates with neoplastic and hyperproliferative conditions of the colorectal mucosa. The specificity of the PNA test for colorectal neoplasia was 76%. Therefore the use of more discriminate carbohydrate probes are needed for the pre-symptomatic detection of colorectal neoplasia.
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PMID:Detection of colorectal neoplasia with peanut-agglutinin (PNA)-reactive carbohydrate structures in rectal mucus. 942 64

CD44 belongs to a family of adhesion molecules displayed by a wide range of normal and malignant cells. Several studies implicated its presence as a marker for poor prognosis or metastases, especially in breast and colon cancer. CD44 has been proposed as an invasion marker for glioblastoma. We studied 75 astrocytic tumors with different degrees of anaplasia including juvenile pilocytic astrocytoma (JPA), low-grade astrocytoma (LGA), anaplastic astrocytoma (AA), and glioblastoma multiforme (GBM) to determine whether standard CD44 (CD44s) can be used as a clinically useful marker distinguishing between low- and high-grade gliomas. Archival paraffin-embedded tissues from 19 JPAs, 20 LGAs, 17 AAs, and 19 GBMs were immunostained with standard CD44 monoclonal antibody and compared with glial fibrillary acidic protein, using the streptavidin-complex peroxidase technique. Immunostaining was rated on a three-tiered scale by two observers. The expression of variant-splice forms of CD44 (CD44v) have been variably reported in brain tumors; a subset of these gliomas were tested with anti-CD44v monoclonal antibodies. In the tumors studied, 89% of JPAs, 90% of LGAs, 76% of AAs, and 84% of GBMs have 2+ or 3+ intensity for CD44s. Low- and high-grade gliomas showed no significant difference in staining (P > .05). Therefore, CD44s does not seem to correlate with the grading range of astrocytomas. The overall intensity of CD44s immunostaining usually, but not always, showed concordance with glial fibrillary acidic protein immunostaining, but the distinctive membrane staining of CD44s surface staining revealed fine cytologic detail in tumor cell processes in diagnostic sections. Some very anaplastic tumors were negative for CD44s, and gliomas were immunonegative for CD44v6. If variant chains (CD44v) are not found in gliomas and if this large series of low- and high-grade gliomas show no difference in CD44 expression, other factors must be explored to understand the differential behavior of low- and high-grade astrocytomas.
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PMID:CD44 expression in astrocytic tumors. 943 70

Inactivation of the p53 tumor suppressor protein has been observed in a large number of human cancers. Overexpression of p53 induces either growth arrest or programmed cell death (apoptosis). The growth arrest function of p53 is mediated by induction of p21 (WAF1/CIP1), but the mechanisms underlying p53-dependent apoptosis are still largely unknown. To investigate these mechanisms, we have identified six differentially expressed transcripts in a human colon cancer cell line undergoing p53-dependent apoptosis. One of the p53-responsive genes showed significant homology to Drosophila peroxidasin, an extracellular matrix-associated peroxidase, and is likely to be its human homologue. Our results suggest a possible connection between p53-dependent apoptosis and the production of reactive oxygen species.
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PMID:Isolation of differentially expressed cDNAs from p53-dependent apoptotic cells: activation of the human homologue of the Drosophila peroxidasin gene. 1044 17

Signal amplification techniques greatly enhance the sensitivity of immunohistochemical (IHC) and in situ hybridization (ISH) methods. In particular, catalyzed signal amplification (CSA) using labeled tyramide or Nanogold-silver staining is an important signal amplification tool. We have applied a combination of both techniques, as has been introduced for ISH, for a further increase in sensitivity of an IHC method to detect cathepsin B. This lysosomal proteinase can also be expressed extracellularly, particularly in relation to cancer metastasis. Higher sensitivity of the IHC method was needed because existing methods failed to demonstrate cathepsin B protein where cathepsin B activity was found with a fluorescence enzyme histochemical method. Combined CSA and Nanogold-silver staining provided the sensitivity that was required. Moreover, this signal amplification method enabled the use of a 10-fold lower concentration of primary antibody (1 microg/ml). Nonspecific background staining was low provided that endogenous biotin, avidin, and peroxidase were completely blocked. The method was reproducible when all steps, and particularly the silver enhancement step, were rigidly controlled. The method resulted in localization patterns of cathepsin B protein that were in agreement with those of cathepsin B activity in serial sections of rat liver containing colon cancer metastases. We concluded that combined application of CSA and Nanogold-silver staining provides high sensitivity for immunohistochemical methods and that activity localization by an enzyme histochemical method is a very attractive alternative to IHC localization of an enzyme because it is at least as sensitive, it is rapid and simple, and it provides direct information on the function of an enzyme.
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PMID:Signal amplification in immunohistochemistry at the light microscopic level using biotinylated tyramide and nanogold-silver staining. 1085 70

The prostaglandin endoperoxide H synthases-1 and 2 (PGHS-1 and PGHS-2; also cyclooxygenases-1 and 2, COX-1 and COX-2) catalyze the committed step in prostaglandin synthesis. PGHS-1 and 2 are of particular interest because they are the major targets of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin, ibuprofen, and the new COX-2 inhibitors. Inhibition of the PGHSs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces fatal thrombotic events, as well as the development of colon cancer and Alzheimer's disease. In this review, we examine how the structures of these enzymes relate mechanistically to cyclooxygenase and peroxidase catalysis, and how differences in the structure of PGHS-2 confer on this isozyme differential sensitivity to COX-2 inhibitors. We further examine the evidence for independent signaling by PGHS-1 and PGHS-2, and the complex mechanisms for regulation of PGHS-2 gene expression.
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PMID:Cyclooxygenases: structural, cellular, and molecular biology. 1096 56

Studies on the role of genetically polymorphic enzymes like cytochrome P450 1A1, arylamine N-acetyltransferase 2 or glutathione S-transferase M1 as cancer susceptibility factors date back more than 20 years, and some associations have been confirmed in several studies and meta-analyses. Overall, the extent of risk modulation due to these polymorphisms is only moderate but remains epidemiologically relevant. The role of some of these polymorphisms in human health may even be ambiguous: rapid acetylation, for example, protects from urinary bladder cancer but appears to increase the risk of laryngeal, lung and colon cancer. The first genetic polymorphisms in xenobiotics transporters such as P-gp (MDR1) and MRP2 have recently been identified. These polymorphisms may have great impact as cancer susceptibility factors as well as factors modulating the outcome of cancer treatment. Enzymes involved in generation or detoxification of reactive oxygen species also have to be considered; one of these enzymes, myeloperoxidase, constitutes a relatively strong lung cancer risk factor, as confirmed in 4 independent studies. Other genes, including those coding for DNA repair enzymes, signal transduction and cell growth regulation, may ultimately prove more important than the metabolic enzymes as cancer susceptibility factors. Study designs in molecular genetic epidemiology are evolving; large ongoing prospective trials increasingly allow confirmatory nested case control studies to be performed. However, carefully controlled, large case-control studies will remain the mainstay in molecular genetic epidemiology. Molecular genetic epidemiological evaluation of response to chemoprevention as well as response to the adverse events of cancer chemotherapy are likely to provide results that may be useful for individualized prevention and treatment in the near future. Since routine genotyping of all persons is now feasible, something like a genotype passport may soon become reality, and molecular and clinical epidemiological studies will have to provide the basis for understanding how to use genotype data for the benefit of the population.
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PMID:Molecular genetics of cancer susceptibility. 1097 Dec 8


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