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)

Monoclonal antibody AM-3 detects a mucin sugar epitope (AM-3 epitope) the expression of which increases in the course of human colon carcinogenesis parallel to the gradual morphological alterations (so called adenoma-carcinoma sequence). In the present report the AM-3-positive mucin has been purified from human normal and carcinomatous colonic tissue. About 300-fold enrichment of the epitope per protein from both sources was achieved after ultracentrifugation, gel filtration on Sepharose CL-6B and isopyknic gradient centrifugation. Slot-blot and enzyme-linked immunosorbent assays of the purified preparation indicated not only different amounts of the mucins but also a consistent qualitative difference between the molecules from both sources. The qualitative difference could be obliterated by a partial removal of the AM-3 epitope from the tumor-derived mucin with neuraminidase. The visualization of the molecules by rotary shadowing indicated that the mucins from both sources have similar length distribution, 80% of the molecules being 100-600 nm long. The reaction with AM-3 antibody followed by rotary shadowing showed that in the purified preparations more than 95% of the tumor-derived molecules and 74% of the normal colon tissue-derived molecules carried the epitope. The tumor-derived mucins bound, on the average, 34 +/- 15 (SD) antibodies/1000 nm of the protein core while the mucin from normal colon tissue carried 12 +/- 11 antibodies/1000 nm of the protein core. These data indicate that the increased expression of AM-3 epitopes during malignant transformation of the human colon is due to accumulation of AM-3-positive mucin as well as a higher number of accessible AM-3 epitopes on this mucin.
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PMID:Increased number of accessible sugar epitopes defined with monoclonal antibody AM-3 on colonic mucins is associated with malignant transformation of colonic mucosa. 171 48

The expression of sialyl-Tn and Tn antigens in various benign, borderline, and malignant ovarian tumors was examined immunohistochemically using newly developed antibodies specific for sialyl-Tn and Tn antigens. Sialyl-Tn antigen was detected in only one benign tumor, a mucinous adenoma that showed faint cytoplasmic staining in a few cells. However, sialyl-Tn was present in 5 of 12 serous borderline tumors, 10 of 19 mucinous borderline tumors, 10 of 13 serous adenocarcinomas, 15 of 16 mucinous adenocarcinomas, 14 of 15 endometrioid adenocarcinomas, and 7 of 7 clear cell carcinomas of the ovary. The antigen expression was observed throughout the cytoplasm of cancer cells and in the apical cytoplasm and luminal contents of some glands. The incidence and intensity of staining for sialyl-Tn antigen were higher in malignant tumors than in borderline tumors, but these results did not correlate with the histologic classification or differentiation. Coexpression of sialyl-Tn antigen and Tn antigen was observed in two serous adenocarcinomas, six mucinous borderline tumors, five mucinous adenocarcinomas, eight endometrioid, and seven clear cell carcinomas. In no case was Tn antigen expressed without concomitant sialyl-Tn antigen expression. Accumulation of sialyl-Tn antigen seems to be an early event of carcinogenesis of the ovary.
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PMID:Expression of Tn and sialyl-Tn antigens in tumor tissues of the ovary. 172 Sep 22

To additionally understand the molecular mechanisms and biologic indicators of colonic tumorigenesis through the adenoma-carcinoma sequence, protein kinase C (PKC) activity was examined in the cytosol and particulate fraction of specimen homogenates from 18 human colonic carcinomas and seven coexisting colonic adenomas and was compared with the adjacent normal mucosal tissues. This study showed that PKC activity could be detected precisely using mini DEAE-Sephacel column purification and histone III-S as a substrate. The PKC activity in both colonic adenoma and carcinoma progressively was reduced in the particulate fraction compared with that of the adjacent normal mucosa from each patient (74.9 +/- 11.3 and 42.4 +/- 9.37 versus 112 +/- 16.8 pmol/min/mg, P less than 0.001), although PKC activity in the cytosolic fraction was not significantly different (62.6 +/- 17.7 and 63.1 +/- 8.08 versus 56.4 +/- 7.32 pmol/min/mg) with respect to protein concentration. Both colonic adenomas and carcinomas showed a significant progressive decrease in total particulate PKC activity compared with the adjacent normal mucosa of each patient (13.5 +/- 2.18 and 7.64 +/- 1.35 versus 19.8 +/- 2.74 pmol/min/g tissue, P less than 0.001) and no difference in total cytosolic PKC activity (15.2 +/- 3.80 and 16.5 +/- 2.02 versus 14.6 +/- 1.81 pmol/min/g tissue). Among PKC activities in carcinomas, there was no difference related to histologic type, Dukes' staging, or carcinoembryonic antigen values. Among PKC activities in colonic adenomas, a significant decrease in particulate PKC correlated with size. The specific PKC activity in the particulate fraction decreased with advancing adenoma size (P less than 0.05). This study showed that colonic carcinogenesis might be associated with alterations in cellular levels of PKC activity and that the decrease in particulate PKC activity in the adenoma had a possible correlation with adenoma size.
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PMID:Protein kinase C activity in human colonic adenoma and colorectal carcinoma. 172 70

We have been studying a rat model of colon cancer in which tumors are induced by direct application of N-methyl-N-nitrosourea (MNU) to discrete areas of the colonic mucosa for a limited period of time. Activation of the ras genes by point mutation has been observed in many experimental tumors, including tumors induced by MNU. To detect potential activating point mutations in the H-ras and K-ras oncogenes in MNU-induced rat colon tumors, DNA samples from 40 adenomas, nine carcinomas, and 14 histologically normal tissue samples from 14 rats--as well as from 16 foci induced on NIH3T3 cells by tumor DNAs--were amplified by the polymerase chain reaction and hybridized with allele-specific oligonucleotide probes. No H-ras point mutations were observed in any of these samples. We did detect K-ras point mutations, however, in four primary tumours--one adenoma (2.5%) and three carcinomas (33%); these mutations were all G----A transitions at the second nucleotide of codons 12 and 13. The absence of detectable ras mutations from the majority of tumors suggests that, in contrast to other animal models utilizing MNU, tumorigenesis in MNU-induced rat colon tumors may predominantly involve activation of genes other than ras.
Carcinogenesis 1992 Jan
PMID:K-ras oncogene mutations in rat colon tumors induced by N-methyl-N-nitrosourea. 173 72

Using the thyroid follicular cell as a model for multi-stage carcinogenesis, we have investigated the role of two potential negative growth regulators ('anti-oncogenes') in epithelial tumour progression--transforming growth factor-beta 1 (TGF beta 1) and p53. Normal follicular cells, as expected, showed marked growth inhibition in response to TGF beta 1. Adenoma cells were equally inhibited. In contrast, spontaneously and SV40-immortalised follicular cell lines showing features of malignant transformation (notably loss of growth factor dependence) had lost all responsiveness to TGF beta 1, accompanied by a partial loss of its receptors. p53 protein was below detectable limits in normal and in adenoma cells but in contrast very high levels were observed in all three transformed lines. In the SV40-immortalised cells, this was expected in view of the known stabilising effect of the viral large T protein. In the spontaneous line we found strong evidence for point mutation of p53, which is known to have the same effect. Both mechanisms result in loss of p53 tumour suppressor function despite increased protein content. We conclude that loss of inhibition by TGF beta and inactivation of p53 are important steps in in vitro immortalisation and/or in vivo tumour progression in human thyroid follicular cells, and speculate that p53 may mediate or be required for the inhibitory signal normally induced by TGF beta 1.
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PMID:Correlated abnormalities of transforming growth factor-beta 1 response and p53 expression in thyroid epithelial cell transformation. 182 Sep 69

Renal adenocarcinoma was induced in CBA/H/T6J mice by a single intraperitoneal injection of 250 mg/kg of streptozotocin (STZ). Light and electron microscopic examination revealed that the carcinoma was a granular cell type-adenocarcinoma with abundant microvilli, basal lamina and intermediate junction indicating an epithelial cell origin. In histopathological analysis of the process of this carcinogenesis, all of the kidneys examined had a dilatation of proximal tubules in the second month and thereafter. In the fifth month, one of eight kidneys developed an adenoma. The adenoma was found in all the kidneys after the ninth month. An adenocarcinoma developed in one of the 14 kidneys in the twelfth month and in all others in the fifteenth month. In vivo labeling of bromodeoxyuridine on the cells in various stages demonstrated an increase of the labeling index which paralleled with progression of the carcinogenesis process. This finding in in vivo analysis of cell proliferation also supports the idea that serial changes of the kidney which are histopathologically proven correspond to the carcinogenesis process. The original carcinoma (STZ-RCC) has serially been passed in vivo at the present. Intrasplenic injection of STZ-RCC yielded multiple macroscopic foci of metastasis in the liver. This indicates that STZ-RCC has a malignant potential. Thus, STZ-induced mouse renal adenocarcinoma can be applied to the model system to investigate carcinogenesis and biological behaviors of renal cell carcinoma.
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PMID:[Histopathological analysis of chemical carcinogenesis process by streptozotocin in the mouse kidney]. 183 79

An epithelial cell line designated FPCK-1 has been established from a tubular adenoma developing in a male familial polyposis coli (FPC) patient. The FPCK-1 cells grow very slowly with abundant mucus production and have been maintained stably for 3 years in culture. No growth was evident either in soft agar or nude mice. FPCK-1 cells present a normal male karyotype and do not show loss of specific loci on chromosomes 5, 17, 18, and 22 which have been reported to be lost frequently in human colon carcinomas. The cells have neither a point mutation on codon 12 of K-ras gene nor gene amplification of myc, c-H-ras, and/or c-K-ras genes. These results thus suggest the existence of hitherto unknown causative event(s) underlying adenoma development in FPC patients. The FPCK-1 cell line should prove useful for further analytical investigation of the multiple steps involved in human colon carcinogenesis.
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PMID:Establishment and characterization of an epithelial cell line with quasi-normal chromosomes from a tubular adenoma of a familial polyposis coli patient. 184 43

Patients with familial adenomatous polyposis have an excess risk for adenomas and cancers of the upper and lower gastrointestinal tract. In the upper intestine these lesions occur mainly around the ampulla of Vater and they parallel mucosal exposure to bile. In view of this finding and of evidence that bile acids play a role in colorectal carcinogenesis, biliary bile acid profiles were determined in 29 patients with familial adenomatous polyposis (12 before colectomy, 17 after colectomy) and in 28 patients without familial adenomatous polyposis (all with colons in situ). Patients with familial adenomatous polyposis had a higher total biliary bile acid concentration than the others. The bile of patients with polyposis had a greater proportion of chenodeoxycholic acid and a lower proportion of deoxycholic acid than did the bile of patients without polyposis. The ratio of chenodeoxycholic acid and its metabolite lithocholic acid to cholic acid and its metabolite deoxycholic acid, which is related to subsequent bile acid profiles in the colon, was higher in patients with polyposis. Because bile acids influence cellular proliferation, these findings may be of importance with respect to intestinal adenoma and cancer growth.
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PMID:Biliary bile acid profiles in familial adenomatous polyposis. 131 Jun 32

The growth of three non-tumorigenic human colonic adenoma cell lines, designated AA/C1, RG/C2 and RR/C1, was inhibited by low concentrations of transforming growth factor beta (TGF-beta) (0.05-0.5 ng ml-1). However, the growth of five human colon cancer cell lines under identical conditions was resistant to high concentrations of TGF-beta (2-10 ng ml-1). This is the first report of well-characterized premalignant human colonic cells showing sensitivity to TGF-beta. The TGF-beta-sensitive adenoma cell line AA/C1 was derived from a relatively large adenoma with a K-ras gene mutation and represents a relatively late-stage adenoma, indicating that loss of response to TGF-beta occurs at a relatively late stage in colorectal carcinogenesis and that the presence of a ras gene mutation does not necessarily confer resistance to TGF-beta. Of further interest, the RG/CZ cell line has a p53 mutation showing that p53 mutations do not necessarily lead to TGF-B insensitivity. Furthermore, in this paper we show that the conversion of the AA/C1 adenoma cell line to a tumorigenic phenotype [Williams et al., (1990) Cancer Res., 50, 4724] is accompanied by a reduced response to the growth-inhibitory effects of TGF-beta up to 10 ng ml-1. Reduced responsiveness to the inhibitory effects of TGF-beta may be an important event in the loss of growth control in colorectal carcinogenesis.
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PMID:Differential sensitivity of human colonic adenoma and carcinoma cells to transforming growth factor beta (TGF-beta): conversion of an adenoma cell line to a tumorigenic phenotype is accompanied by a reduced response to the inhibitory effects of TGF-beta. 188 18

The modifying potential of capsaicin (CAP) on lesion development was examined in a rat multiorgan carcinogenesis model. Groups 1 and 2 were treated sequentially with diethylnitrosamine (DEN) (100 mg/kg, ip, single dose at commencement), N-methylnitrosourea (MNU) (20 mg/kg, ip, 4 doses at days 2, 5, 8, and 11), and N,N-dibutylnitrosamine (DBN) (0.05% in drinking water during weeks 3 and 4). Group 3 received vehicles without carcinogens during the initiation period. Group 4 served as the untreated control. After this initiating procedure, Groups 2 and 3 were administered a diet containing 0.01% CAP. All surviving animals were killed 20 weeks after the beginning of the experiment and the target organs examined histopathologically. The induction of GST-P+ hepatic foci in rats treated with carcinogens was significantly inhibited by treatment with CAP. CAP treatment significantly decreased the incidence of adenoma of the lung but increased the incidence of papillary or nodular (PN) hyperplasia of the urinary bladder. The tumor incidence of other organs, such as the kidney and thyroid, was not significantly different from the corresponding controls. These results demonstrated that concurrent treatment with CAP not only can inhibit carcinogenesis but can also enhance it depending on the organ. Thus, this wide-spectrum initiation model could be used to confirm organ-specific modification potential and, in addition, demonstrate different modifying effects of CAP on liver, lung, and bladder carcinogenesis.
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PMID:Different modifying responses of capsaicin in a wide-spectrum initiation model of F344 rat. 188 47


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