Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the effects of plasma and of cumene hydroperoxide (CUM) on adenosine diphosphate ribosyl transferase (ADPRT) from mononuclear leukocytes (HML) of patients with colonic adenomatous polyps (n = 22), with colonic hyperplastic polyps (n = 5) and with neither type of polyp (controls) (n = 6). ADPRT was measured after incubation of HML with plasma alone (termed the plasma value), and with plasma plus CUM (50 microM) (the activated value); the difference elicited by CUM was termed the induced value. There was no significant difference in values between the control and hyperplastic polyp groups: these were combined for further analysis. The plasma (P = 0.038), activated (P = 0.009) and induced (P = 0.0024) values of the combined group all differed significantly from those of the adenoma group. At low exposures, CUM stimulated both ADPRT and unscheduled DNA synthesis and, at higher exposures, inactivated both. Pretreatment of HML with vitamin E protected against these effects of CUM, while pretreatment with diamide (which depletes GSH) accentuated the effects. This study demonstrates a differential reaction of ADPRT in patients harboring colonic adenomas and suggests that the origin of this difference may lie in cellular responses to oxidative stress.
Carcinogenesis 1988 Mar
PMID:Effects of cumene hydroperoxide on adenosine diphosphate ribosyl transferase in mononuclear leukocytes of patients with adenomatous polyps in the colon. 312 91

Preneoplastic mucosal changes were studied at six different time-points during dimethylhydrazine (DMH)-induced colorectal carcinogenesis in the rat. After 40 weeks of treatment, seven of 10 animals were bearing a total of 11 colorectal adenocarcinomas. The crypt cell production rate in the normal mucosa of DMH-treated animals was greatly increased in the left colon and rectum and further rose with the duration of the experiment. Focal disturbances of the mucosal architecture could be detected as early as 4 weeks after the initiation of DMH-treatment using a stereomicroscope. Their incidence was greatest in the left colon and rectum and increased strongly with the duration of carcinogen exposure. Characterization of these mucosal alterations, by means of conventional histology, morphometry after microdissection, cell kinetics, mucin histochemistry and quantitative enzyme histochemistry performed with serial sections, revealed mild epithelial dysplasia, a considerable elongation and dilatation of the crypts and a marked increase of the crypt cell production, including a shift of the main proliferative compartment from the basal to the medial crypt segment as well as the occurrence of mitotic figures in the luminal epithelium. In affected crypts, the goblet cells completely lacked sulphomucins and exclusively contained sialomucins. The activities of the enzymes diaminopeptidase IV (brush-border), succinate dehydrogenase (mitochondria) and acid beta-galactosidase (lysosomes) were markedly reduced. We conclude that these early mucosal alterations are indeed preneoplastic lesions and indicate the existence of the adenoma-carcinoma sequence in this animal model.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of stereomicroscopically identified preneoplastic lesions during dimethylhydrazine-induced colonic carcinogenesis. 314 93

To study the behavior of the tumor-associated antigens CEA and CA 19-9 in colorectal carcinogenesis, exemplified by the adenoma-carcinoma sequence, their tissue concentrations were measured in adenomas of different size and histology and compared with those found in normal colonic mucosa and carcinoma. Both in the case of monoclonal and polyclonal CEA assay, significantly higher concentrations were found in the adenoma tissue as compared with normal mucosa. Carcinomas revealed, on average, an even higher tissue CEA level, but the concentrations measured showed considerable scatter. In the adenoma group, the villous lesions and those with severe cellular atypia were characterized by markedly higher CEA concentrations, reflecting their special position in the adenoma-carcinoma sequence. In the case of CA 19-9, too, an increase in tissue concentrations from normal mucosa through adenoma to carcinoma was observed. In contrast, among the adenomas of different histologies and dysplasia no differences were observed. These findings fit with the concept of the adenoma-carcinoma sequence which, in our opinion, represents a suitable model for studying the significance of tumor-associated antigens in the carcinogenesis of colorectal cancer and its precursors.
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PMID:Tissue concentrations of CEA and CA 19-9 in the carcinogenesis of colorectal carcinoma exemplified by the adenoma-carcinoma sequence. 316 15

The preneoplastic events occurring in the mucosa of patients at risk of developing colonic cancer are described and correlate well with the histogenesis of an adenoma. Confirmatory evidence from experimental carcinogenesis systems is provided. Among individuals at 50% risk of colon cancer, proliferative abnormalities relating to the distribution of S-phase cells are present. Aging, whether among the high-risk or the unaffected control population, appears to bring about enhancement of the percentage of DNA-synthesizing cells in the crypts, indicating a similar response of colonic epithelial cells to environmental conditions over time. The combination of an already existing defect in cell proliferation among those at high risk of familial colon cancer along with an elevated rate of cell renewal increases the probability that a neoplasm will arise in this population.
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PMID:Cell proliferation and colonic neoplasia. 322 20

In an endoscopic population screening study for detection of colorectal polyps the diet was registered before ascertaining whether polyps were present. Polyps less than 5 mm in diameter were followed up for 2 years before removal and histologic diagnosis. The relative risk of an increase both in the volume of registered adenomas (excluding new adenomas) and in the total mass of adenomas (including new adenomas) showed a trend towards an inverse relationship with intake of dietary fiber, non-fiber carbohydrate, and cruciferous vegetables, reaching the significance level only for intake of dietary fiber for increase of adenoma volume in men. A trend towards a positive relationship between growth and total fat intake was more inconsistent, although the significance level was reached for the relative risk of increase in adenoma mass for men. These prospective observations with regard to polyp-bearing individuals agree with previous incidence and prevalence data that have indicated a relationship between dietary habits and colorectal carcinogenesis.
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PMID:Colorectal adenomas and food. A prospective study of change in volume and total mass of adenomas in man. 324 23

A group of 44 rats underwent the equivalent of a ureterosigmoidostomy (US), while a second group of 18 rats underwent a pediculated graft (PG) of urothelial tissue in the sigmoid wall. Histological lesions were observed in the colon near the bladder colon junction in US rats exclusively. These lesions included dysplasias (5/23), cystic glands (4/23) and 10 neoplasms (9/23), three of which were adenomas, showing elements of juvenile polyp and tubular adenoma in one case. The seven other tumors showed typical histological features of colonic adenocarcinomas, but no frank evidence of parietal tumoral invasion was observed and their cancerous nature was questionable. It is probably a true carcinogenesis since we induced the same histological changes as those in the mucosae adjacent to colonic adenocarcinomas after human US surgery. Moreover, by immunoperoxidase using antibodies against mucus associated antigens (M1 and M3C antigens) we demonstrated that US rat carcinogenesis differs from dimethylhydrazine (DMH) rat carcinogenesis. Furthermore, our results suggest that urine may be an important factor in inducing this type of US carcinogenesis.
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PMID:Rat colonic carcinogenesis after ureterosigmoidostomy: pathogenesis and immunohistological study. 328 98

In the present study, eight organosulfur compounds from garlic and onions were studied for their inhibitory effects on benzo[a]pyrene (BP)-induced neoplasia of forestomach and lung of female A/J mice when administered 96 and 48 h prior to carcinogen challenge. These compounds had one, two or three linearly connected sulfur atoms. They included the four allyl group-containing derivatives: allyl methyl trisulfide (AMT), allyl methyl disulfide (AMD), diallyl trisulfide (DAT), and diallyl sulfide (DAS), and also four corresponding saturated compounds in which propyl groups were substituted for the allyl groups. All four allylic compounds inhibited BP-induced neoplasia of the forestomach. The saturated analogs were almost without inhibitory activity, indicating the importance of the allyl groups. DAT, which contains two allyl groups, was more potent than AMT, which contains only one allyl group, thus providing further evidence for the role of allyl groups in the inhibitory effects observed. DAS and AMD, but not DAT or AMT, inhibited pulmonary adenoma formation. The fact that in the lung the monosulfide and disulfide inhibited, but the trisulfide did not inhibit, indicates that the number of sulfur atoms in the molecule can control the organ sites at which protection against carcinogenesis will occur. All four allylic compounds induced increased glutathione S-transferase (GST) activity in the forestomach, but varied in their capacity to induce GST in lung, liver and small bowel. Their saturated analogs produced little or no induction. In evaluating relationships between diet and cancer, it would be useful to consider the possible role of garlic and onion organosulfur compounds as protective agents. In addition, further studies of this class of chemicals might lead to the identification and development of useful new chemopreventive compounds.
Carcinogenesis 1988 Jan
PMID:Effects of organosulfur compounds from garlic and onions on benzo[a]pyrene-induced neoplasia and glutathione S-transferase activity in the mouse. 333 37

We have used an indirect immunofluorescence assay to demonstrate the cell membrane expression of carcinoembryonic antigen (CEA) by a pre-malignant colorectal adenoma derived epithelial cell line (PC/AA) and three colorectal carcinoma cell lines (HT29, PC/JW and PC/JW/FI). The results obtained indicated that CEA may be used as a marker for tumour progression up to the point of malignant transformation, after which the selection for anaplastic variants during continuous in vitro culture may result in the subsequent reduction of cell membrane CEA expression. The percentage of PC/AA cells expressing cell membrane CEA increased from 23.1% of diploid early passage (passage 18) cells to 56.0% of aneuploid late passage (passage 58) cells. Although non-tumorigenic, the proportion of PC/AA cells expressing cell membrane CEA at late passage corresponded to that for the PC/JW carcinoma line (56.2%) and is further evidence for the progression of PC/AA in culture. A 3T3 feeder-independent variant of PC/JW (PC/JW/FI) demonstrated a similar percentage of CEA-positive cells as the parental line for the first 21 passages without feeder support, but by passage 27 without 3T3 feeders only 35.3% of cells stained positive. This could be restored to 62.0% by continuous treatment with sodium butyrate (2 mM). A differential growth response to sodium butyrate was noted for the pre-malignant adenoma cell line PC/AA and the carcinoma lines HT29 and PC/JW/FI. Concentrations of sodium butyrate (2 mM) that killed early passage PC/AA cells allowed the late passage PC/AA cells and the carcinoma lines to proliferate, raising the possibility of sodium butyrate acting as a tumour promotor in the human colorectum.
Carcinogenesis 1988 Mar
PMID:Expression of carcinoembryonic antigen by adenoma and carcinoma derived epithelial cell lines: possible marker of tumour progression and modulation of expression by sodium butyrate. 334 82

The entire colonic mucosa of 51 cases of colorectal carcinoma was examined histologically. Mucosal lesions including goblet cell hyperplasia, crypt dilatation, ulceration with regeneration, basal cell hyperplasia, metaplastic lesions, and adenomas were encountered. Goblet cell hyperplasia (80.4%) was most prominent adjacent to the carcinoma (transitional mucosa). Whether this represents a precancerous change is controversial. Crypt dilatation (57%) is considered a nonspecific change due to mucosal injury and indicates obstruction to the outlet of the crypts. Ulceration (6%) is often proximal to the carcinoma and is considered secondary to stasis and ischaemia due to obstruction. Basal cell hyperplasia is particularly prominent at the site of lymphoid follicles. It is suggested that the hyperplasia is a reactive response to the presence of stimuli in the intestinal content. It is observed that metaplastic lesions have their origin from these foci of basal cell hyperplasia. The presence of basal cell hyperplasia in metaplastic polyps (14%) indicates that they are active lesions in the process of formation and growth. The occurrence of metaplastic lesions may provide an indication of an adverse environment and a vulnerable mucosa. Adenomas have their origin from basal cells of colonic crypts. They are present in 47% of colorectal carcinoma. The findings support the view that adenomas are the most common and important precursor lesion associated with colorectal carcinoma in man. No de novo foci of malignant transformation was encountered but this does not exclude the possibility of de novo carcinogenesis of the colorectum.
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PMID:Background mucosal changes in colorectal carcinomas. 334 20

A non-tumorigenic epithelial cell line designated PC/AA, derived from a large pre-malignant colorectal adenoma from a patient with familial polyposis coli (also referred to as hereditary adenomatosis of the colon and rectum) has become immortal in vitro. PC/AA has been passaged in vitro continuously for over 4 years and shows no signs of senescence. At early passage, PC/AA has a normal diploid karyotype but with late passage is showing signs of progression, becoming aneuploid and displaying signs of morphological transformation. Every cell examined of late-passage PC/AA has an isochromosome (1q), and one other marker chromosome which is probably derived from an additional chromosome 8. The majority of cells examined have 48 chromosomes. Despite showing signs of progression in vitro, late-passage PC/AA has remained non-tumorigenic in athymic nude mice and retained morphological differentiation characteristics of colonic cells, in particular the ability to synthesize and secrete mucin. Two other cell lines derived from small adenomas did not become immortal in vitro and were also non-tumorigenic in athymic nude mice. The isolation of an immortal pre-malignant human epithelial cell line could prove invaluable in studies on human carcinogenesis and tumour progression. Our results, showing that only a large adenoma and no small adenomas have given rise to immortal cell lines, raise the possibility that the acquisition of in vitro immortality is associated with a relatively late stage in the adenoma-carcinoma sequence. The possible involvement of chromosome 1 in tumour progression is discussed.
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PMID:Immortalization of a human colorectal adenoma cell line by continuous in vitro passage: possible involvement of chromosome 1 in tumour progression. 337 63


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